# pos

id: cord-287123-ldkuwcc7
pos: CD
token:
  3-phenyl-1-((R)-1-(3-phenyl-1-((S)-1-(3-phenylureido)propan-2-yl)ureido)hexan-2-yl)-1-(4-phenylbutyl)urea

lemma:
  3-phenyl-1-((r)-1-(3-phenyl-1-((s)-1-(3-phenylureido)propan-2-yl)ureido)hexan-2-yl)-1-(4-phenylbutyl)urea


id: cord-287123-ldkuwcc7
pos: NNP
token:
  R)-4-(cyclohexylmethyl)-5-(4hydroxybenzyl)-1-((R)-1-((S)-2-(((S)-6-isopropyl-2,3-dioxopiperazin-1-yl)methyl)pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl)piperazine-2,3-dione

lemma:
  R)-4-(cyclohexylmethyl)-5-(4hydroxybenzyl)-1-((R)-1-((S)-2-(((S)-6-isopropyl-2,3-dioxopiperazin-1-yl)methyl)pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl)piperazine-2,3-dione


# ent

id: cord-000264-o80duxhs
type: PROTEIN
entity:
  orosomucoid 8 a 2 macroglobulin apolipoprotein A1 apolipoprotein C3 glutathione peroxidase 3 plasma retinol binding protein


id: cord-001677-p6ikd8ns
type: CHEMICAL
entity:
  ethylenediaminetetraacetic acid EDTA pH 8 0 7 5 µl of 20 sodium dodecyl sulfate SDS 1 5 µl of Proteinase K


id: cord-000947-psguw47w
type: WORK_OF_ART
entity:
  A Study of the Mechanism of the Chaperone like Function of an scFv of Human Creatine Kinase by Computer Simulation date 2013 04


id: cord-000947-psguw47w
type: WORK_OF_ART
entity:
  Chaperone Like Effect of the Linker on the Isolated C Terminal Domain of Rabbit Muscle Creatine Kinase Protease


id: cord-003033-nlaiurau
type: PROTEIN
entity:
  interferon gamma MAPK Mitogen activated protein kinase ERK extracellular signal regulated kinase AKT serine threonine protein kinase PMN


id: cord-003033-nlaiurau
type: ORG
entity:
  the American College of Cardiology Foundation American Heart Association Task Force on Practice Guidelines


id: cord-009492-lhwhkada
type: CHEMICAL
entity:
  BGE constituents perfluorinated carboxylic acids trifluoroacetic pentafluoropropionic heptafluorobutyric


id: cord-013952-zp4q3ztr
type: PROTEIN
entity:
  specificity mitogen activated protein kinase kinase 1 2 PKCε protein kinase C epsilon type MLCK myosin light chain kinase MLC myosin light chain PLC phospholipase C IP 3 inositol trisphosphate SR sarcoplasmic reticulum AQP2 aquaporin 2 BP


id: cord-013952-zp4q3ztr
type: GGP
entity:
  protein kinase kinase 1 2 PKCε protein kinase C epsilon type MLCK myosin light chain kinase MLC myosin light chain PLC phospholipase C IP 3 inositol trisphosphate SR sarcoplasmic reticulum AQP2 aquaporin 2


id: cord-011184-ohdukhqt
type: GGP
entity:
  thiazolidinediones alpha glucosidase inhibitors sulphonylurea dipeptidyl peptidase IV DPP IV inhibitors sodium glucose cotransporter 2 SGLT 2 inhibitors


id: cord-011184-ohdukhqt
type: GGP
entity:
  Alpha glucosidase inhibitors b Alpha amylase inhibitors c Dipeptidyl peptidase IV inhibitors d Inhibitors


id: cord-007735-ejvv2lxv
type: PROTEIN
entity:
  Tumour necrosis factor alpha MHC1 Major histocompatibility complex class 1 BAL Bronchoalveolar lavage 1


id: cord-018401-josb16pi
type: PROTEIN
entity:
  Ac V 6 R 2 NH 2 Ac V 6 K 2 NH 2 Ac A 6 K NH 2 Ac I 6 K 2 NH 2 Ac A 6 K OH DA 6 NH 2 Ac V 6 D 2 NH 2 Ac A 6 D OH KA 6 NH 2


id: cord-018401-josb16pi
type: GGP
entity:
  Surface plasmon resonance spectroscopy Atomic force microscopy Investigation of the kinetics of self assembly conduct structure manipulation determine the size and morphology of the nanostructures


id: cord-018401-josb16pi
type: CHEMICAL
entity:
  aromatic p stacking between the aromatic rings of the pyrenyl structure dominates At neutral pH though the amino


id: cord-024193-khdvj6t5
type: PROTEIN
entity:
  Pro Q Diamond Life Technologies a fluorescent dye that had been validated to bind specifically to phosphorylated residues


id: cord-031957-df4luh5v
type: CHEMICAL
entity:
  defensin like antifungal peptide from Trigonella foenum graecum fenugreek seeds Antimicrobial peptides pore formers


id: cord-031957-df4luh5v
type: CHEMICAL
entity:
  stinging nettle Urtica dioica rhizomes Hevein like antimicrobial peptides of plants Structural basis for chitin


id: cord-048360-n9sih438
type: WORK_OF_ART
entity:
  The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum Crossreactive


id: cord-103421-46owvqw8
type: PROTEIN
entity:
  NCBI Identical Protein Groups IPG Database using taxon sequence identifiers SI Table 4 The IPG Database


id: cord-254404-lrsqrc2u
type: PROTEIN
entity:
  H sapiens NPY type D melanogaster NPF type H sapiens PrRP type and D melanogaster sNPF type receptors


id: cord-254404-lrsqrc2u
type: TAXON
entity:
  S mediterranea Schmidtea mediterranea C gigas Crassostrea gigas D melanogaster Drosophila melanogaster C elegans Caenorhabditis elegans


id: cord-254404-lrsqrc2u
type: CHEMICAL
entity:
  rubens Asterias rubens P dumerilii Platynereis dumerilii L stagnalis Lymnaea stagnalis M expansa Moniezia expansa S mediterranea Schmidtea mediterranea C gigas Crassostrea gigas D melanogaster Drosophila melanogaster C elegans Caenorhabditis


id: cord-254404-lrsqrc2u
type: CHEMICAL
entity:
  D melanogaster GenBank AAF51909 3 a PrRP type receptor from H sapiens NP_004239 1 and sNPF type receptors from D melanogaster GenBank NP_524176 1 and C gigas GenBank XP_011451552 1 as query sequences A


id: cord-260392-hj9s5cnu
type: CELL_LINE
entity:
  MCF 7 cells IC 50 2 7 mM and 3 4 mM respectively was also analo gous to that of B campestris antifungal peptide IC 50 5 8 mM and 1 6


id: cord-260392-hj9s5cnu
type: CHEMICAL
entity:
  B campestris antifungal peptides 17 exhibit antifungal activity The remaining two proteins 5 21 manifest trypsin


id: cord-260392-hj9s5cnu
type: CHEMICAL
entity:
  B campestris antifungal peptide IC 50 5 8 mM and 1 6 mM respectively Both kale and B campestris antifungal peptide


id: cord-022955-vy0qgtll
type: PROTEIN
entity:
  brainspecific metalloprotease M Teufel Biochemistry Exploratory Research Sanofi Aventis Strasbourg France E


id: cord-022955-vy0qgtll
type: CELL_TYPE
entity:
  human B lymphocytes E Janas 1 R Priest 1 S Ratcliffe 2 and R Malhotra 1 1 Rheumatoid Arthritis Biology GlaxoSmithKline Stevenage UK 2 High Throughput Chemistry GlaxoSmithKline Stevenage UK E


id: cord-022955-vy0qgtll
type: PROTEIN
entity:
  zinc chelator Y Tamada 1 T Nakajima 1 T R Shearer 2 and M Azuma 1 2 1 Research Laboratories Senju Pharmaceutical Co Ltd


id: cord-022955-vy0qgtll
type: PROTEIN
entity:
  tissue type plasminogen activator t PA plasminogen activator inhibitor PAI 1 plasminogen a2 antiplasmin


id: cord-022955-vy0qgtll
type: ORG
entity:
  F Sannier Laboratory of Biotechnology and Bioorganic Chemistry University of La Rochelle La Rochelle


id: cord-022955-vy0qgtll
type: ORG
entity:
  Group Hungarian Academy of Sciences Budapest Hungary 3 Department of Biochemistry University of Oxford Oxford


id: cord-022955-vy0qgtll
type: ORG
entity:
  K Troulinaki Institute of Molecular Biology and Biotechnology Foundation for Research and Technology


id: cord-022955-vy0qgtll
type: CHEMICAL
entity:
  auxins 2 4 Dichlorophenoxyacetic acid 2 4 D 4 amino 3 5 6 Trichloropiridin 2 carboxilic acid Picloram Indoleacetic acid IAA


id: cord-022955-vy0qgtll
type: CHEMICAL
entity:
  Chernova 1 K D Allen 2 E P Tennant 2 K D Wilkinson 1 and Y O Chernoff 2 1 Department of Biochemistry Emory


id: cord-103837-iuvigqdx
type: PROTEIN
entity:
  SARS Cov 2 spike protein ECD peptides S1 Subunit 1 S2 Subunit 2 NTD N Terminal Domain RBD Receptor Binding Domain CTD C Terminal Domain A


id: cord-103837-iuvigqdx
type: DNA
entity:
  consensus cluster S1 Subunit 1 S2 Subunit 2 NTD N Terminal Domain RBD Receptor Binding Domain CTD C Terminal Domain


id: cord-103837-iuvigqdx
type: FAC
entity:
  the CD4 sup sup Th Cell Response in Spontaneously Controlled Hepatitis C Virus Infection Includes Dominant


id: cord-262748-v4xue7ha
type: ORG
entity:
  proteinprotein interfaces Dissection of Specific and Non specific Protein Protein Interfaces Dissecting


id: cord-274101-vm9nh8lc
type: PROTEIN
entity:
  heparan c 2012 Institute of Food Technologists Vol 11 2012 r Comprehensive Reviews in Food Science and Food Safety 193 sulfate molecules


id: cord-274101-vm9nh8lc
type: CL
entity:
  monocytogenes E coli O157 H7 and Salmonella Typhimurium Sivarooban and others 2008 The activity of bacteriocins incorporated into polymeric materials in synergy with other conservation technologies has also been reported Films incorporated with enterocins A and B bacteriocins produced by Enterococcus faecium


id: cord-262253-3ovqhypt
type: DNA
entity:
  Neuron Front Alziemer s Disease and Periodontal Disease Bidirectional Interrelationships Infectious immunity


id: cord-262253-3ovqhypt
type: GGP
entity:
  Alzheimer s disease AD making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease


id: cord-262253-3ovqhypt
type: GGP
entity:
  Alzheimer s disease A multicenter blinded randomized factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer s


id: cord-262253-3ovqhypt
type: CHEMICAL
entity:
  amyloid beta A4 precursor protein binding family APBB2 clusterin CLU and gamma secretase subunit presenilin 1 PSEN1 61 Similarly


id: cord-262253-3ovqhypt
type: CHEMICAL
entity:
  amyloid beta peptide Regulation of APP cleavage by alpha beta and gamma secretases Amyloid beta Structure biology and structure based


id: cord-269462-7yozebv2
type: ORG
entity:
  Viral Fusion Peptides Induce Several Signal Transduction Pathway Activations That Are Essential for Interleukin 10


id: cord-305755-6jup93v4
type: WORK_OF_ART
entity:
  A Report of 1014 Cases Chest CT for Typical 2019 nCoV Pneumonia Relationship to Negative RT PCR Testing Diagnosing


id: cord-314604-w61sqy17
type: ORG
entity:
  Loops that Mediate Protein Protein Interactions and Translation into Submicromolar Inhibitors Intramolecular


id: cord-314604-w61sqy17
type: WORK_OF_ART
entity:
  Helix Folding A Joint Experimental and Simulation Study Design of a Short Thermally Stable Helix Embedded in a Macrocycle


id: cord-315115-f61xcnuw
type: ORG
entity:
  Amphibian Antimicrobial Peptides Uncovers Multiple Length Dependent Correlations for Peptide Design and Prediction date


id: cord-315115-f61xcnuw
type: ORG
entity:
  Multifunctional Antimicrobial Peptides A Review of Their Pharmacology Effectivity Mechanism of Action and Possible Future Directions


id: cord-315115-f61xcnuw
type: ORG
entity:
  Structural Analysis of Amphibian Insect and Plant Host Defense Peptides Inspires the Design of Novel Therapeutic Molecules In Host Defense Peptides


id: cord-315115-f61xcnuw
type: ORG
entity:
  Specifically Attack Bacterial Computer Aided Design of Antimicrobial Peptides Are We Generating Effective Drug Candidates Front Database


id: cord-300189-gsp1dozg
type: CELL_LINE
entity:
  H144 H145 H146 H147 H148 H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15 H16 H17 H18 H19 H20 H21 H22 H23 H24 H25 H26 H27 H28 H29 H30 H31 H32 H33 H34 H35 H36 H37 H38 H39 H40 H41 H42 H43 H44 H45 H46 H47 H48 H49 H50 H51 H52 H53 H54 H55 H56 H57 H58 H59 H60 H61 H62 H63 H64 H65 H66 H67 H68 H69 H70 H71 H72 H73 H74 H75 H76 H77 H78 H79 H80 H131 H132 H133 H134 H135 H136 H137 H138 H139 H140 H121 H122 H123 H124 H125 H126 H127 H128 H129 H130 H111 H112 H113 H114 H115 H116 H117 H118 H119 H120 H101 H102 H103 H104 H105 H106 H107 H108 H109 H110 H91 H92 H93 H94 H95 H96 H97 H98 H99 H100 H81 H82 H83 H84 H85 H86 H87 H88


id: cord-023208-w99gc5nx
type: PROTEIN
entity:
  crude peptides H Lys Thr Asn Met Lys His Met b Ala Gly b Ala Ala Ala b Ala Gly b Ala Val Val b Gly Gly b Leu Gly OH b 1 b Th120 EFFICIENT


id: cord-023208-w99gc5nx
type: CELL_TYPE
entity:
  blood cells G Bai 1 P Gomes 1 R Seixas 1 M Hicks 2 M Prieto 3 M Bastos 1 Eukaryotic antibiotic peptides


id: cord-023208-w99gc5nx
type: PROTEIN
entity:
  cyclic β2 3 amino acids 1S 2S 1R 2R ACHC and 1S 2S 1R 2R ACPC Low temperature 233 K 1H NMR spectra in CD3OD


id: cord-023208-w99gc5nx
type: PROTEIN
entity:
  N Terminus His Phe Arg and Trp Positions 2 Department of Experimental and Health Sciences Graduate School of Pharmaceutical Sciences 2 Graduate School of Agriculture 3 Graduate School of Medicine


id: cord-023208-w99gc5nx
type: GGP
entity:
  isopropylidenedicyclohexane 4 4 disubstituted bicyclohexane 1 4 disubstituted cyclohexane 1 5 disubstituted cyclooctane and 1 2 1 3


id: cord-023208-w99gc5nx
type: GGP
entity:
  PKA PKC Ca2 channel activators classical regulatory peptides bradykinin somatostatin Met enkephalin endothelin neurotensin


id: cord-023208-w99gc5nx
type: CHEBI
entity:
  amino acid protein stromal cell derived factor 1α SDF 1α 1 One strategy for the treatment of these diseases could be to block the interaction between CXCR4 and SDF 1α with small CXCR4


id: cord-023208-w99gc5nx
type: GGP
entity:
  Tyr 4 SO3H Thr Gln OH II H D Phe 4 SO3H Ile Tyr 4 SO3H Thr Gln OH III H Tyr Ile Tyr 4 SO3H Thr Gln OH IV H Tyr 4 SO3H Ile Tyr Thr Gln OH V


id: cord-023208-w99gc5nx
type: GGP
entity:
  human i e cholic acid CA chenodeoxycholic acid CDCA deoxycholic acid DCA ursodeoxycholic acid UDCA and lithocholic acid


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  His Met b Ala Gly b Ala Ala Ala b Ala Gly b Ala Val Val b Gly Gly b Leu Gly OH b 1 b Th120 EFFICIENT


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  4 4 disubstituted isopropylidenedicyclohexane 4 4 disubstituted bicyclohexane 1 4 disubstituted cyclohexane 1 5 disubstituted cyclooctane


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  dehydropeptides Gly ZPhe AbuPO OMe 2 Gly ZPhe AlaPO OEt 2 Gly ZPhe LeuPO OMe 2 Gly ZPhe ValPO OEt 2 Gly ZPhe


id: cord-023208-w99gc5nx
type: CHEMICAL
entity:
  D β Peptide molecules possess interesting conformational characteristics and biological properties They


id: cord-257494-242k58ll
type: PROTEIN
entity:
  major histocompatibility complex class I like hereditary hemochromatosis protein HFE transferrin receptor 2


id: cord-257494-242k58ll
type: CL
entity:
  mutans C albicans Eikenella corrodens Actinobacillus actinomycetemcomitans Streptococcus pneumoniae Haemophilus influenzae Streptococcus pyogenes Bacteroides fragilis E coli


id: cord-023225-5quigar4
type: PROTEIN
entity:
  Glycyl tRNA Synthetase S R Stone 1 K Hoffmann 1 2 N Milech 1 2 P T Cunningham 1 M Kerfoot 1 S Winslow 1 Y F Tan 1 M Anastasas 1 C Hall 1 M Scobie 1 P Watt 2 and R Hopkins 1 2 1 Drug Discovery Technology Unit Telethon Institute for Child Health Research 100 Roberts Road Subicao 6008 Western Australia 2 Phylogica Pty Ltd 100 Roberts Road Subiaco 6008 Western Australia Biopanning


id: cord-023225-5quigar4
type: PROTEIN
entity:
  linear covalent structure Ac Aib Asn Leu Aib Pro Ala Val Aib Pro Aib Leu Aib Pro Leuol Ac acetyl Aib


id: cord-023225-5quigar4
type: PROTEIN
entity:
  Leishmania major C Servis H Zalila I Gonzalez L Lozano N Fasel Department of Biochemistry University of Lausanne


id: cord-023225-5quigar4
type: GGP
entity:
  S S Ac Ser ΨH CF3 Pro NHMe and R S Ac Ser Ψ CF3 HPro NHMe 4 Their thermodynamic and kinetic features


id: cord-023225-5quigar4
type: ORG
entity:
  A Girard E Biron Faculty of Pharmacy Université Laval and CHUQ Research Center Quebec Canada Combinatorial


id: cord-023225-5quigar4
type: ORG
entity:
  Haute Normandie PRIMACEN Institute for Medical Research and Innovation IRIB University of Rouen 76821


id: cord-023225-5quigar4
type: CHEMICAL
entity:
  betaamyloid toxicity 1 2 Aggregated βA causes many pathological changes in cultures of mixed neurons and astrocytes such as sporadic cytoplasmic intracellular Ca 2 signal activation of reactive oxygen


id: cord-023225-5quigar4
type: CHEMICAL
entity:
  N terminal extremity 1 probably this insertion on another portion of the peptide provides a change in the conformation of the molecule and its hydrophobic cluster


id: cord-023225-5quigar4
type: CHEMICAL
entity:
  N N isopropylidene derivatives of Ser Thr containing dipeptides 3 We found the reaction of mannopyranosyl trichloroacetimidate


id: cord-316792-89f8g0m8
type: GGP
entity:
  platelet receptors von Willebrand disease type B a missense mutation selectively abolishes ristocetin induced von Willebrand factor binding


id: cord-331633-ix5un6c9
type: ORG
entity:
  Antimicrobial Agents An Overview Self Assembly of Antimicrobial Peptides on Gold Nanodots Against Multidrug Resistant Bacteria


id: cord-291534-c6cjxq07
type: DISEASE
entity:
  influenza A virus and surfactant protein D Mechanism of adenovirus neutralization by human alpha defensins Epithelial defensins impair adenoviral infection


id: cord-291534-c6cjxq07
type: DISEASE
entity:
  respiratory syncytial virus infected human alveolar macrophages Antiviral activity of human beta defensin 3


id: cord-269756-tid8a464
type: PROTEIN
entity:
  phospholipids 1 palmitoyl 2 hydroxy sn glycero 3 phosphocholine LPC 1 2 dipalmitoyl snglycero phosphatidylcholine DPPC 1 2 dipalmitoyl sn glycero 3 phospho 1


id: cord-269756-tid8a464
type: GGP
entity:
  POPA S 0 0 29 Those differences in the TMA orientation are likely due to distinct orienting forces that arise from the particular hydrogen bonding


id: cord-269756-tid8a464
type: ORG
entity:
  Membrane Surface Order An Electron Spin Resonance Study HIV gp41 Fusion Peptide Increases Membrane Ordering


id: cord-269756-tid8a464
type: ORG
entity:
  Pulsed Electron Paramagnetic Resonance of Spin Labels Investigation of Model Membrane Disruption Mechanism


id: cord-269756-tid8a464
type: ORG
entity:
  Kinetics and Activation Thermodynamics of Stalk and Pore Formation Differently Mechanistic Implications Conformation


id: cord-269756-tid8a464
type: CHEMICAL
entity:
  glycerol POPG 1 palmitoyl 2 oleoyl sn glycero 3 phospho L serine POPS 1 palmitoyl 2 oleoyl sn glycero 3 phosphate POPA


id: cord-295207-0p6x4lwx
type: PROTEIN
entity:
  class III viral fusion proteins domain I green domain II yellow domain III blue domain IV stem domain indigo Figure 1


id: cord-295207-0p6x4lwx
type: DISEASE
entity:
  herpes simplex virus type 1 gB 1 28 and Epstein Barr virus gB into class III viral fusion proteins VFP 29


id: cord-280383-hi7z3nob
type: DNA
entity:
  isotype control antibody 36 H445 V458 P459 F460 S461 P462 D463 G464 K465 P466 C467 T468 P469 P470 A471 L472 N473 C474 Y475 R426 S432 Y436 K439 Y440 Y442 P469 P470 A471 L472 C474 Y475 W476 L478 N479 D480 G482 Y484 T485 T486 T487 G488 Y491 Q492 L443 R444 H445 I455 S456 N457 V458 P459 F460 S461 P462 D463 G464 K465 P466 C467 T468 P469 P470 A471 L472 N473 C474 Y475 b12 I108 C109 S110 L111 D113 Q114 S115 L116 K117 P118 C119 V120 P206 K207 V208 S209 F210 E211 P212 I213 P214 I251 R252 P253 I424 N425 M426 W427 C428 K429 V430 N280 A281 S365 G366 G367 D368 P369 I371 V372 T373 Y384 N386 P417 R419 V430 G431 K432 T455 R456 G472 G473 D474 M475 W95 T232 F233 N234 T236 S257 L260 N262 G263 S264 L265 A266 E267 E268 E269 V270 V271 T290 S291 S364 S365 G366 G367 D368 P369 E370 I371 V372 T373 T450 S481 3 4 Cautions


id: cord-287123-ldkuwcc7
type: CHEMICAL
entity:
  N substituted benzimidazoles pyridazin 3 2H ones chiral pyridazines N phenylureas chiral 3 1H indol 3 yl 2 3 4 nitrophenyl ureido propanamides 2 N Piperazinyl acetamide derivatives quinazolinones


id: cord-307909-7vbxyns0
type: CHEBI
entity:
  amino acid nucleotide base recognition Simple intuitive calculations of free energy of binding for protein ligand complexes 1


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  villin headpiece miniprotein Stanislaw Oldziej 1 Wioletta _ Zmudzi nska 1 Anna Hałabis 1 1 The C terminal subdomain


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  human glucose 6 phosphate dehydrogenase G6PD Nurriza Ab Latif 1 2 Paul Engel 1 1 Conway Institute Univerversity College Dublin 2 Faculty of Biosciences and Medical Engineering Universiti Teknologi Malaysia Human glucose 6 phosphate dehydrogenase G6PD


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  coagulation factor VIIa Jais R Bjelke 1 Gorm Andersen 1 Henrik Østergaard 1 Laust B Johnsen 1 Anette A Pedersen 1 Tina H Glue 1 1


id: cord-001835-0s7ok4uw
type: PROTEIN
entity:
  enoyl CoA hydratase family Fernandes 1 Teresa Sorbo 2 Ivan Duka 2 Lia Christina Appold 3 Marianne Ilbert 4 Fabian Kiessling 3 CNRS UMR 7281 5 UCiBio REQUIMTE


id: cord-001835-0s7ok4uw
type: GGP
entity:
  Biryukova 1 Elizaveta Kostanova 1 Alexey Kononikhin 0 Anna Bugrova 1 Evgeny Nikolaev 0 Mark Rosenfeld 1 1 N M


id: cord-001835-0s7ok4uw
type: ORG
entity:
  School of Chemistry National University of Ireland Galway 2 School of Biochemistry and Immunology Trinity College


id: cord-001835-0s7ok4uw
type: WORK_OF_ART
entity:
  Destabilizing the Transient Helical Conformation of Islet Amyloid Polypeptide Hastens Peptide Self Assembly and Potentiates Cytotoxicity Carole Anne de Carufel 1


id: cord-001835-0s7ok4uw
type: EVENT
entity:
  Physical and Engineering Biology Yale University 3 Mechanical Engineering and Materials Science Yale University 4 Applied Physics Yale University


id: cord-001835-0s7ok4uw
type: ORG
entity:
  Department of Biology Stanford University 2 Department of Pediatrics Stanford University 3 Department of Pharmacology University of California San Diego 4 Department of Pediatrics Emory University 5 Institute for Biomedical Sciences


id: cord-001835-0s7ok4uw
type: ORG
entity:
  Graduate School of Science and Engineering Ibaraki University 3 Department of Life Science Graduate School of Life Science University of Hyogo 4


id: cord-001835-0s7ok4uw
type: ORG
entity:
  The New York Structural Biology Center 5 Department of Biochemistry Faculty of Medicine University of Montreal


id: cord-001835-0s7ok4uw
type: ORG
entity:
  University of Southern California Keck School of Medicine 2 Developing a Technique to Detect Deamidated Proteins


id: cord-001835-0s7ok4uw
type: ORG
entity:
  the Ethical Committee for Animal Experimentation from Center of Health and Science of the Federal University of Rio de Janeiro


id: cord-001835-0s7ok4uw
type: ORG
entity:
  1 National Autonomous University of Mexico Faculty of Medicine 2 National Autonomous University of Mexico Faculty of Chemistry 3


id: cord-001835-0s7ok4uw
type: WORK_OF_ART
entity:
  Deartment of Biology Wilfrid Laurier University 2 Department of Biology University of Waterloo Chloroplast


id: cord-001835-0s7ok4uw
type: ORG
entity:
  University of Greenwich Faculty of Engineering and Sciene 2 University of Greenwich Centre of Sports Science and Human Performance


id: cord-001835-0s7ok4uw
type: CHEMICAL
entity:
  N terminal recognition element In addition expressed protein ligation is being used to incorporate backbone modifications such as the thioamide


id: cord-001835-0s7ok4uw
type: CHEMICAL
entity:
  N terminal catalytic module 2 This module shows the capacity of recognize the GlcNAc MurNAc L Ala D isoGln muropeptide GMDP


id: cord-001835-0s7ok4uw
type: DISEASE
entity:
  acute myeloid leukemia mutations Daniela Marasco 1 Concetta Di Natale 1 Valentina Punzo 1 Domenico Riccardi 1 Pasqualina Scognamiglio 1 Roberta Cascella 2 Cristina Cecchi 2 Fabrizio Chiti 2 Marilisa Leone


id: cord-001835-0s7ok4uw
type: DISEASE
entity:
  human immunodeficiency virus type 1 subtype C based on Envelope V3 sequences Available http istree bioprotection org Signal processing based Bioinformatics methods


id: cord-333262-xvfl7ycj
type: ORG
entity:
  the Wuhan Seafood Market Coronavirus Possible Importance of the KRSFIEDLLFNKV Motif Structure Function and Evolution of Coronavirus Spike Proteins Cleavage


id: cord-333262-xvfl7ycj
type: WORK_OF_ART
entity:
  Peptides Corresponding to the Predicted Heptad Repeat 2 Domain of the Feline Coronavirus Spike Protein


id: cord-333262-xvfl7ycj
type: PERCENT
entity:
  2 HR2 Derived Peptide Entry Inhibition as a Result of Mutations in the HR1 Domain of the Spike Fusion Protein Peptides as Drugs The Journey so Far Prediction of HIV Vaccine Synthetic Peptides Related To HIV Env Proteins


id: cord-333262-xvfl7ycj
type: ORG
entity:
  INRA EUC Rapport Programming Environment for the Chemical Pharmaceutical and Biotechnology Industries Computer Aided Design of Biomolecules


id: cord-333262-xvfl7ycj
type: WORK_OF_ART
entity:
  The GOR Method for Predicting Secondary Structure in Proteins in Prediction of Protein Structure and the Principles of Protein Conformation Synthesis


id: cord-333262-xvfl7ycj
type: ORG
entity:
  Towards Automated Reasoning for Drug Discovery and Pharmaceutical Business Intelligence Towards New Tools for Pharmacoepidemiology The Concept of Novel Compositions of Matter A Theoretical Analysis Suggestions


id: cord-333262-xvfl7ycj
type: ORG
entity:
  Inference Language for Medicine Continuity of Patient Care with PCAST Disaggregation Split Complex Numbers and


id: cord-333262-xvfl7ycj
type: ORG
entity:
  the Role of a Smart Web for Precision Medicine Supported by Biobanking Studies in Using a Universal Exchange


id: cord-333262-xvfl7ycj
type: WORK_OF_ART
entity:
  The Engines of Hippocrates From the Dawn of Medicine to Medical and Pharmaceutical Informatics Robson


id: cord-333262-xvfl7ycj
type: DISEASE
entity:
  coronavirus serotypes OC43 like and 229E like which are the main examples discussed below While the common cold


id: cord-333262-xvfl7ycj
type: DISEASE
entity:
  nasal mucosa nasopharynx lung stomach small intestine colon skin lymph nodes thymus bone marrow spleen liver kidney


id: cord-348432-6jgao58w
type: CHEMICAL
entity:
  HPMA N 2 hydroxypropyl methylacrylamide DAMA N N dicarboxymethylaminopropyl methacrylamide MTS 3 4 5 dimethylthiazol 2 yl 5 3 carboxymethoxyphenyl 2 4 sulphophenyl 2H tetrazolium


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  N 1 2 4 dihydroxyphenylacetyl L asparaginyl N 12 L lysyl 4 8 diaza 1 12 dodecanediamine Dhpa Asn Dada 12Lys


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  human neurotensin receptor 1 Neurotensin NT pGlu 1 Leu 2 Tyr 3 Glu 4 Asn 5 Lys 6 Pro 7 Arg 8 Arg 9 Pro 10 Tyr 11 Ile 12 Leu 13


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  S4 13 PV peptide However transfection mediated by the scrambled peptide was signifi cantly less effi cient than that obtained for the


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  B10234 B10238 peptide dimer B9870 Suim D Arg Arg Pro Hyp Gly Igl Ser D Igl Oic Arg 2 Suim suberimidyl


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  hexapeptides B o c A C P C P O A C P O A C A C P C A C P C A C P C O M e B o c A C P C P O A C A C P C P O A C A C P C A C P C O M e Boc


id: cord-023209-un2ysc2v
type: PROTEIN
entity:
  cycilc hexapeptides cyclo L Lys Gly 3 cyclo L Glu Gly 3 cyclo L Lys D Ala 3 cyclo D Glu L Ala 3 cyclo L Trp D Lys 3


id: cord-023209-un2ysc2v
type: GGP
entity:
  neurohypophyseal nonapeptide hormone cycle1 6 H Cys 1 Tyr 2 Phe 3 Gln 4 Asn 5 Cys 6 Pro 7 Arg 8 Gly 9 NH 2


id: cord-023209-un2ysc2v
type: GGP
entity:
  human neurotensin receptor 1 Neurotensin NT pGlu 1 Leu 2 Tyr 3 Glu 4 Asn 5 Lys 6 Pro 7 Arg 8 Arg 9 Pro 10 Tyr 11 Ile


id: cord-023209-un2ysc2v
type: CHEBI
entity:
  proteins nucleophosmin survivin prion and alpha 7 subunit of acetylcholine receptor AChR Nucleophosmin


id: cord-023209-un2ysc2v
type: GGP
entity:
  hexapeptides B o c A C P C P O A C P O A C A C P C A C P C A C P C O M e B o c A C P C P O A C A C P C P O A C A C P C A C P C O M e


id: cord-023209-un2ysc2v
type: ORG
entity:
  Närvänen Ale 1 Equal Contribution 1 University of Kuopio FINLAND 2 University of Helsinki FINLAND Phage


id: cord-023209-un2ysc2v
type: ORG
entity:
  Biochemistry Creighton University Trusova Valeriya Gorbenko Galyna V N Karazin Kharkov National University


id: cord-023209-un2ysc2v
type: CHEMICAL
entity:
  diastereoisomeric cyclic disubstituted amino acids 1S 3S and 1R 3S 1 amino 3 methoxy cyclopentanecarboxylic acid Ac 5 c OM


id: cord-340970-389t032s
type: ORG
entity:
  the Severe Acute Respiratory Syndrome SARS Coronavirus Spike Glycoprotein Perspective for SARS Vaccine Development date 2004


id: cord-339879-92esdjy9
type: PROTEIN
entity:
  anti gp41 human monoclonal antibody Human immunodeficiency virus type 1 neutralizing monoclonal antibody 2F5


id: cord-339879-92esdjy9
type: PROTEIN
entity:
  NHR mimetics Cross reactive human immunodeficiency virus type 1 neutralizing human monoclonal antibody


id: cord-337812-arivkkj0
type: CHEMICAL
entity:
  2 1H benzotriazole 1 yl 1 1 3 3tetramethyluronium hexafluorophosphate HBTU N hydroxybenzotriazole HOBt


id: cord-332003-67e9fchy
type: GGP
entity:
  multidrug resistant Escherichia coli Salmonella enterica Klebsiella pneumoniae and Shigella flexneri


id: cord-337897-hkvll3xh
type: PROTEIN
entity:
  aaa65789 aaa72945 aaa79971 aab27127 baa01583 baa02756 baa03581 baa03905 baa08372 baa09073 baa09075 baa88057 bab08107 caa03854 caa43793 cab46677 gnwvtc


# bib

id: cord-000128-t74b5j2j
author: Laufer, S.D
date: 2008-12-17
txt: ./txt/cord-000128-t74b5j2j.txt
cache: ./cache/cord-000128-t74b5j2j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778081/
doi: 10.2174/138161208786898806
summary:
  In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. The focus of this article is recent progress in the field of peptide-mediated cellular delivery of siRNA and steric block oligonucleotides in cell tissue culture as a starting point for further developments illustrated by own experimental data. In contrast to many noncovalent CPP-mediated siRNA delivery approaches, efficient splice correction was only achieved with conjugates of peptide and steric block oligonucleotide. As outlined above, our quantitative studies along with microscopic analyses of siRNAs and steric block oligonucleotides using either a peptide or a commercially availably cationic lipid as carrier clearly show that less than 0.1% -5% of molecules taken up are involved in a biological response, i.e. RNAimediated down regulation or splice correction-mediated up regulation of reporter gene activity.

title:
  Peptide-Mediated Cellular Delivery of Oligonucleotide-Based Therapeutics In Vitro: Quantitative Evaluation of Overall Efficacy Employing Easy to Handle Reporter Systems

abstract:
  Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.


id: cord-000264-o80duxhs
title: Proteomics: Challenges, Techniques and Possibilities to Overcome Biological Sample Complexity
author: Chandramouli, Kondethimmanahalli
date: 2009-12-08
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950283/
doi: 10.4061/2009/239204
abstract:
  Proteomics is the large-scale study of the structure and function of proteins in complex biological sample. Such an approach has the potential value to understand the complex nature of the organism. Current proteomic tools allow large-scale, high-throughput analyses for the detection, identification, and functional investigation of proteome. Advances in protein fractionation and labeling techniques have improved protein identification to include the least abundant proteins. In addition, proteomics has been complemented by the analysis of posttranslational modifications and techniques for the quantitative comparison of different proteomes. However, the major limitation of proteomic investigations remains the complexity of biological structures and physiological processes, rendering the path of exploration paved with various difficulties and pitfalls. The quantity of data that is acquired with new techniques places new challenges on data processing and analysis. This article provides a brief overview of currently available proteomic techniques and their applications, followed by detailed description of advantages and technical challenges. Some solutions to circumvent technical difficulties are proposed.


id: cord-000947-psguw47w
author: Feng, Jianyu
date: 2013-04-24
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634753/
doi: 10.1371/journal.pone.0062147
title:
  A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation

abstract:
  A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function.


id: cord-001677-p6ikd8ns
title: Exploration of New Sites in Adenovirus Hexon for Foreign Peptides Insertion
author: Hansra, Satyender
date: 2015-05-29
txt: ./txt/cord-001677-p6ikd8ns.txt
cache: ./cache/cord-001677-p6ikd8ns.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460227/
doi: 10.2174/1874357901509010001
summary:
  To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. In this study, we explored different sites in HVRs 7, 8 and 9 of hAd5 hexon for the insertion of a peptide corresponding to the porcine reproductive and respiratory syndrome virus (PRRSV) main neutralizing epitope B [19] of the GP5 protein. In the current study, we find a new site in HVR7 for incorporation of foreign peptide into hAd5 hexon, and determine that the peptide was also exposed on the virion surface making it readily accessible for antibody binding and be potentially useful for vaccination. Herein, we report a novel adenovirus vector (Ad5HVR7epB) with the insertion of the PRRSV main neutralizing epitope B in 3 different HVR regions of the major capsid protein hexon.

abstract:
  Adenoviral vectors are now being explored as vaccine carriers to prevent infectious diseases in humans and animals. There are two strategies aimed at the expression of a vaccine antigen by adenoviral vectors. The first includes an insertion of the foreign gene expression cassette into the E1 region. The second strategy is antigen incorporation into the viral capsid proteins. To extend this methodology, we have searched for new sites at the human adenovirus serotype 5 major capsid protein hexon for a vaccine antigen insertion. To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. However, we could not rescue the viruses with the insertions of the peptide into HVR 8 and 9, consistent with the viruses being unable to tolerate insertions at these sites. In contrast, the virus with the insertion of the peptide in HVR 7 was viable - growing well in cell culture and the inserted peptide was exposed on the virion surface.


id: cord-001726-d7iwkatn
author: Henry, Kevin A.
date: 2015-08-04
txt: ./txt/cord-001726-d7iwkatn.txt
cache: ./cache/cord-001726-d7iwkatn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523942/
doi: 10.3389/fmicb.2015.00755
summary:
  Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage''s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage''s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. While in some cases the results of these studies have been promising, antibody epitope-based peptide vaccines are no longer an area of active research for several reasons: (i) in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins (Irving et al., 2010 ; see below); (ii) antibodies against a single epitope may be of limited utility, especially for highly variable pathogens (Van Regenmortel, 2012); and (iii) for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time.

title:
  Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold

abstract:
  For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.


id: cord-001835-0s7ok4uw
title: Abstracts of the 29th Annual Symposium of The Protein Society
author: nan
date: 2015-10-01
txt: ./txt/cord-001835-0s7ok4uw.txt
cache: ./cache/cord-001835-0s7ok4uw.txt
extension: .txt
mime: text/plain
url: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pro.2823
doi: 10.1002/pro.2823
abstract: nan
summary:
  Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues.


id: cord-002141-9mxi4dzi
title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding
author: Memczak, Henry
date: 2016-07-14
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944999/
doi: 10.1371/journal.pone.0159074
abstract:
  Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.


id: cord-002394-n85ptr5p
author: Reddy, Vijayalakshmi
date: 2017-01-26
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5268390/
doi: 10.1371/journal.pntd.0005238
title:
  Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations

abstract:
  BACKGROUND: Chikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia. However, 10–20% affected individuals develop persistent arthralgia which contributes to considerable morbidity. The exact molecular mechanisms underlying these manifestations are not well understood. The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components. METHODOLOGY: Bioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components. Two peptides (A&B) were identified using several bioinformatic tools, synthesised and used to validate the results obtained in silico. An ELISA was designed to assess the immunoreactivity of serum samples from CHIKV patients to these peptides. Further, experiments were conducted in a C57BL/6J experimental mouse model to investigate if peptide A and peptide B were indeed capable of inducing pathology. FINDINGS: The serum samples showed reactivity of varying degrees, indicating that these peptides are indeed being recognized by the host immune system during CHIKV infection. Further, these peptides when injected into C57BL/6J mice were able to induce significant inflammation in the muscles of C57BL/6J mice, similar to that observed in animals that were injected with CHIKV alone. Additionally, animals that were primed initially with CHIKV followed by a subsequent injection of the CHIKV peptides exhibited enhanced inflammatory pathology in the skeletal muscles as compared to animals that were injected with peptides or virus alone. Collectively these observations validate the hypothesis that molecular mimicry between CHIKV E1 protein and host proteins does contribute to pathology in CHIKV infection.


id: cord-003020-q69f57el
title: Computer-aided design of amino acid-based therapeutics: a review
author: Farhadi, Tayebeh
date: 2018-05-14
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958949/
doi: 10.2147/dddt.s159767
abstract:
  During the last two decades, the pharmaceutical industry has progressed from detecting small molecules to designing biologic-based therapeutics. Amino acid-based drugs are a group of biologic-based therapeutics that can effectively combat the diseases caused by drug resistance or molecular deficiency. Computational techniques play a key role to design and develop the amino acid-based therapeutics such as proteins, peptides and peptidomimetics. In this study, it was attempted to discuss the various elements for computational design of amino acid-based therapeutics. Protein design seeks to identify the properties of amino acid sequences that fold to predetermined structures with desirable structural and functional characteristics. Peptide drugs occupy a middle space between proteins and small molecules and it is hoped that they can target “undruggable” intracellular protein–protein interactions. Peptidomimetics, the compounds that mimic the biologic characteristics of peptides, present refined pharmacokinetic properties compared to the original peptides. Here, the elaborated techniques that are developed to characterize the amino acid sequences consistent with a specific structure and allow protein design are discussed. Moreover, the key principles and recent advances in currently introduced computational techniques for rational peptide design are spotlighted. The most advanced computational techniques developed to design novel peptidomimetics are also summarized.


id: cord-003033-nlaiurau
title: Therapeutic Potential of Annexin A1 in Ischemia Reperfusion Injury
author: Ansari, Junaid
date: 2018-04-16
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979321/
doi: 10.3390/ijms19041211
abstract:
  Cardiovascular disease (CVD) continues to be the leading cause of death in the world. Increased inflammation and an enhanced thrombotic milieu represent two major complications of CVD, which can culminate into an ischemic event. Treatment for these life-threatening complications remains reperfusion and restoration of blood flow. However, reperfusion strategies may result in ischemia–reperfusion injury (I/RI) secondary to various cardiovascular pathologies, including myocardial infarction and stroke, by furthering the inflammatory and thrombotic responses and delivering inflammatory mediators to the affected tissue. Annexin A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro-resolving mediators, known to have significant effects in resolving inflammation in a variety of disease models. Mounting evidence suggests that AnxA1, which interacts with the formyl peptide receptor (FPR) family, may have a significant role in mitigating I/RI associated complications. In this review article, we focus on how AnxA1 plays a protective role in the I/R based vascular pathologies.


id: cord-003084-y4w3plro
title: Cell-Penetrating Peptides to Enhance Delivery of Oligonucleotide-Based Therapeutics
author: McClorey, Graham
date: 2018-05-05
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027240/
doi: 10.3390/biomedicines6020051
abstract:
  The promise of nucleic acid based oligonucleotides as effective genetic therapies has been held back by their low bioavailability and poor cellular uptake to target tissues upon systemic administration. One such strategy to improve upon delivery is the use of short cell-penetrating peptides (CPPs) that can be either directly attached to their cargo through covalent linkages or through the formation of noncovalent nanoparticle complexes that can facilitate cellular uptake. In this review, we will highlight recent proof-of-principle studies that have utilized both of these strategies to improve nucleic acid delivery and discuss the prospects for translation of this approach for clinical application.


id: cord-003948-npijn7co
author: Esfandiyari, Reza
date: 2019-10-23
txt: ./txt/cord-003948-npijn7co.txt
cache: ./cache/cord-003948-npijn7co.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820248/
doi: 10.1016/j.heliyon.2019.e02652
summary:
  title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells mesenchymal stem cells (MSCs) are key to produce antimicrobial peptides and to inhibit the growth of pathogens. The purpose of this review was to investigate the targets and mechanisms of antimicrobial peptides secreted by MSCs. Antibiotics are used to treat bacterial infections through either inhibiting or killing the target bacteria. Recent studies have found that MSCs play an important role in the treatment of diseases, including infections, by producing antimicrobial peptides [12, 13, 14] . Due to the unique characteristics of antimicrobial peptides, these peptides are one of the main candidates in the treatment of bacterial diseases and are effective on antibiotic resistant strains and even cancer cells. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37

title:
  Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells

abstract:
  Peptides are secreted by different cell types and are trendy therapeutic agents that have attracted attention for the treatment of several diseases such as infections. Antimicrobial peptides exert various mechanisms such as changing cell membrane permeability which leads to inhibition or death of bacterial cells. mesenchymal stem cells (MSCs) are key to produce antimicrobial peptides and to inhibit the growth of pathogens. These cells have been shown to be capable of producing antimicrobial peptides upon exposure to different bacteria. As a result, antimicrobial peptides can be considered as novel agents for the treatment of infectious diseases. The purpose of this review was to investigate the targets and mechanisms of antimicrobial peptides secreted by MSCs.


id: cord-007735-ejvv2lxv
title: Immunomodulatory Properties of Defensins and Cathelicidins
author: Bowdish, D. M. E.
date: 2006
txt: ./txt/cord-007735-ejvv2lxv.txt
cache: ./cache/cord-007735-ejvv2lxv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121507/
doi: 10.1007/3-540-29916-5_2
summary:
  The expression of certain β-defensins is inducible upon stimulation with bacterial components or pro-inflammatory cytokines and thus these peptides are presumed to be an important component of host defence to infection or inflammation. The difficulties in assessing the role of host defence peptides in vivo are profound, as it is almost impossible to account for synergistic interactions between peptides and other factors, to assess the actual concentrations at the sites of infection and to discriminate the direct antimicrobial activity of peptides from other less direct effects such as enhancement of inflammatory mechanisms (chemotaxis and recruitment of effector cells, enhancement of nonopsonic phagocytosis, etc.). It appears that host defence peptides induce chemotaxis in two ways: first through direct chemotactic activity of PMNs and mononuclear cells mediated through CCR6 and other as yet to be identified receptors and second through inducing chemokine production which would hypothetically increase the numbers of neutrophils and monocytes at sites of infection.

abstract:
  Host defence peptides are a conserved component of the innate immune response in all complex life forms. In humans, the major classes of host defence peptides include the α- and β-defensins and the cathelicidin, hCAP-18/LL-37. These peptides are expressed in the granules of neutrophils and by a wide variety of tissue types. They have many roles in the immune response including both indirect and direct antimicrobial activity, the ability to act as chemokines as well as induce chemokine production leading to recruitment of leukocytes to the site of infection, the promotion of wound healing and an ability to modulate adaptive immunity. It appears that many of these properties are mediated though direct interaction of peptides with the cells of the innate immune response including monocytes, dendritic cells, T cells and epithelial cells. The importance of these peptides in immune responses has been demonstrated since animals defective in the expression of certain host defence peptides showgreater susceptibility to bacterial infections. In the very few instances in which human patients have been demonstrated to have defective host defence peptide expression, these individuals suffer from frequent infections. Although studies of the immunomodulatory properties of these peptides are in their infancy, there is a growing body of evidence suggesting that the immunomodulatory properties of these small, naturally occurring molecules might be harnessed for development as novel therapeutic agents.


id: cord-007755-o2r8ktie
author: Kokoszka, Malgorzata E.
date: 2014-10-20
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122165/
doi: 10.1007/978-1-4939-2020-4_12
title:
  Mapping Protein–Protein Interactions with Phage-Displayed Combinatorial Peptide Libraries and Alanine Scanning

abstract:
  One avenue for inferring the function of a protein is to learn what proteins it may bind to in the cell. Among the various methodologies, one way for doing so is to affinity select peptide ligands from a phage-displayed combinatorial peptide library and then to examine if the proteins that carry such peptide sequences interact with the target protein in the cell. With the protocols described in this chapter, a laboratory with skills in microbiology, molecular biology, and protein biochemistry can readily identify peptides in the library that bind selectively, and with micromolar affinity, to a given target protein on the time scale of 2 months. To illustrate this approach, we use a library of bacteriophage M13 particles, which display 12-mer combinatorial peptides, to affinity select different peptide ligands for two different targets, the SH3 domain of the human Lyn protein tyrosine kinase and a segment of the yeast serine/threonine protein kinase Cbk1. The binding properties of the selected peptide ligands are then dissected by sequence alignment, Kunkel mutagenesis, and alanine scanning. Finally, the peptide ligands can be used to predict cellular interacting proteins and serve as the starting point for drug discovery.


id: cord-009492-lhwhkada
title: Recent developments in CE and CEC of peptides
author: Kašička, Václav
date: 2007-11-28
txt: ./txt/cord-009492-lhwhkada.txt
cache: ./cache/cord-009492-lhwhkada.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159161/
doi: 10.1002/elps.200700550
summary:
  Novel developments in individual CE and CEC modes are shown and several types of their applications to peptide analysis are presented: conventional qualitative and quantitative analysis, purity control, determination in biomatrices, monitoring of chemical and enzymatical reactions and physical changes, amino acid and sequence analysis, and peptide mapping of proteins. Preconcentration and preseparation (or "sample cleanup") are the necessary operations for sample preparations, when separation power and/or sensitivity of CE and CEC are not sufficient for direct analysis of peptides present at low concentration levels and/or in complex mixtures of different (bio)matrices, such as body fluids, cell lysates, and tissue extracts. After optimization the injection conditions, such as type and concentration of the acid and organic solvent in the sample solution, length of the water plug, sample injection time, and separation voltage, more than 3000-fold improvement in detection signal was obtained, permitting analysis of bioactive peptides and tryptic protein digests in low nanomolar (fmol/mL) levels.

abstract:
  The article brings a comprehensive survey of recent developments and applications of high‐performance capillary electromigration methods, zone electrophoresis, ITP, IEF, affinity electrophoresis, EKC, and electrochromatography, to analysis, preparation, and physicochemical characterization of peptides. New approaches to the theoretical description and experimental verification of electromigration behavior of peptides and to methodology of their separations, such as sample preparation, adsorption suppression, and detection, are presented. Novel developments in individual CE and CEC modes are shown and several types of their applications to peptide analysis are presented: conventional qualitative and quantitative analysis, purity control, determination in biomatrices, monitoring of chemical and enzymatical reactions and physical changes, amino acid and sequence analysis, and peptide mapping of proteins. Some examples of micropreparative peptide separations are given and capabilities of CE and CEC techniques to provide important physicochemical characteristics of peptides are demonstrated.


id: cord-009743-2rntyccn
author: Wang, Ke‐Ming
date: 2008-09-10
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164091/
doi: 10.1111/j.1742-4658.2008.06631.x
title:
  Characterization of inhibitory mechanism and antifungal activity between group‐1 and group‐2 phytocystatins from taro (Colocasia esculenta)

abstract:
  Tarocystatin from Colocasia esculenta, a group‐2 phytocystatin, is a defense protein against phytopathogenic nematodes and fungi. It is composed of a highly conserved N‐terminal region, which is homological to group‐1 cystatin, and a repetitive peptide at the C‐terminus. The purified recombinant proteins of tarocystatin, such as full‐length (FL), N‐terminus (Nt) and C‐terminus (Ct) peptides, were produced and their inhibitory activities against papain as well as their antifungal effects were investigated. Kinetic analysis revealed that FL peptide exhibited mixed type inhibition (K (ia) = 0.098 μm and K (ib) = 0.252 μm) and Nt peptide showed competitive inhibition (K (i) = 0.057 μm), whereas Ct peptide possessed weak papain activation properties. A shift in the inhibitory pattern from competitive inhibition of Nt peptide alone to mixed type inhibition of FL peptide implied that the Ct peptide has an regulatory effect on the function of FL peptide. Based on the inhibitory kinetics of FL (group‐2) and Nt (group‐1) peptides on papain activity, an inhibitory mechanism of group‐2 phytocystatins and a regulatory mechanism of extended Ct peptide have each been proposed. By contrast, the antifungal activity of Nt peptide appeared to be greater than that of FL peptide, and the Ct peptide showed no effect on antifungal activity, indicating that the antifungal effect is not related to proteinase inhibitory activity. The results are valid for most phytocystatins with respect to the inhibitory mechanism against cysteine proteinase.


id: cord-011184-ohdukhqt
title: Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes
author: Patil, Shital P.
date: 2019-07-22
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223764/
doi: 10.1007/s10989-019-09899-z
abstract:
  ABSTRACT: Recent advances in analytical techniques have opened new opportunities for plant-based drug discovery in the field of peptide and proteins. Enzymatic hydrolysis of plant parent proteins forms bioactive peptides which are explored in the treatment of various diseases. In this review, we will discuss the identified plant-based bioactive proteins and peptides and the in vitro, in vivo results for the treatment of diabetes. Extraction, isolation, characterization and commercial utilization of plant proteins is a challenge for the pharmaceutical industry as plants contain several interfering secondary metabolites. The market of peptide drugs for the treatment of diabetes is growing at a fast rate. Plant-based bioactive peptides might open up new opportunities to discover economic lead for the management of various diseases. GRAPHIC ABSTRACT: [Image: see text]


id: cord-012391-53hgrs40
title: Anti-Acne Action of Peptides Isolated from Burdock Root—Preliminary Studies and Pilot Testing
author: Miazga-Karska, Malgorzata
date: 2020-04-27
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248785/
doi: 10.3390/molecules25092027
abstract:
  This work aimed to study the anti-bacterial, anti-biofilm and anti-oxidant potential effects of low molecular weight (LMW) peptides (Br-p) isolated from burdock (Arctium lappa L.) roots. We conducted a preliminary study to exclude or confirm the antibiotic activity of the LMW peptides fraction of this plant. Br-p were isolated using gel filtration and a 10 kDa cut-off membrane. The obtained peptides were identified by MALDI TOF/TOF. Antibacterial activity was tested against acne strains using diffusion tests, MIC and MBC. The fibroblast cytotoxicity of Br-p was tested, and the selectivity index (SI) value was determined. The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. One of the Br-p peptides assessed on MALDI RapidDeNovo was LRCDYGRFFASKSLYDPLKKRR cationic peptide. It was analogous to that contained in A. lappa protein, and theoretically it was matched as a peptide with antibiotic nature. Br-p did not show toxicity to fibroblasts in the tested concentration up to 10 mg/mL, obtaining CC(50) 10 mg/mL. The SI value for the tested Propionibacterium strains ranged from 160 to 320. Finally, an active dressing based on chitosan/alginate/genipin was prepared using freeze-drying. The formed dressing was evaluated for its anti-acne activity. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin.


id: cord-013364-pq9obtrc
title: Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
author: Capasso, Domenica
date: 2020-09-19
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570809/
doi: 10.3390/molecules25184298
abstract:
  Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.


id: cord-013952-zp4q3ztr
title: Biosynthesis of lanthionine-constrained agonists of G protein-coupled receptors
author: Moll, Gert N.
date: 2020-10-30
txt: ./txt/cord-013952-zp4q3ztr.txt
cache: ./cache/cord-013952-zp4q3ztr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609037/
doi: 10.1042/bst20200427
summary:
  Biosynthesis of lanthionine-constrained peptides exploiting engineered Gram-positive or Gram-negative bacteria that contain lanthionine-introducing enzymes constitutes a convenient method for discovery of lanthionine-stabilized GPCR agonists. The nisin precursor peptide is dehydrated by the dehydratase NisB [26, 27] , after which a cyclase NisC [28] couples dehydroamino acids to cysteines followed by export by the transporter NisT and removal of the leader peptide by the extracellular leader peptidase NisP [29] . While the attainment of strict rules with respect to the substrate specificities of lanthionine-introducing enzymes has been challenging, some practical guidelines for the design of modifiable peptides have been reached for some lanthipeptide biosynthesis systems [32] . The stereospecificity of NisC-cyclized GPCR agonist, 4,7 lanthionine-angiotensin-(1-7) was investigated using the Ni 2 B method, which opens the ring structure while retaining the D or L conformation [43] . In addition, the feasibility of highthroughput screening for tailor-made lanthionine-introducing enzymes with adapted substrate specificity for rational design and biosynthesis of lanthipeptide GPCR agonists has recently been demonstrated.

abstract:
  The conformation with which natural agonistic peptides interact with G protein-coupled receptor(s) (GPCR(s)) partly results from intramolecular interactions such as hydrogen bridges or is induced by ligand–receptor interactions. The conformational freedom of a peptide can be constrained by intramolecular cross-links. Conformational constraints enhance the receptor specificity, may lead to biased activity and confer proteolytic resistance to peptidic GPCR agonists. Chemical synthesis allows to introduce a variety of cross-links into a peptide and is suitable for bulk production of relatively simple lead peptides. Lanthionines are thioether bridged alanines of which the two alanines can be introduced at different distances in chosen positions in a peptide. Thioether bridges are much more stable than disulfide bridges. Biosynthesis of lanthionine-constrained peptides exploiting engineered Gram-positive or Gram-negative bacteria that contain lanthionine-introducing enzymes constitutes a convenient method for discovery of lanthionine-stabilized GPCR agonists. The presence of an N-terminal leader peptide enables dehydratases to dehydrate serines and threonines in the peptide of interest after which a cyclase can couple the formed dehydroamino acids to cysteines forming (methyl)lanthionines. The leader peptide also guides the export of the formed lanthionine-containing precursor peptide out of Gram-positive bacteria via a lanthipeptide transporter. An engineered cleavage site in the C-terminus of the leader peptide allows to cleave off the leader peptide yielding the modified peptide of interest. Lanthipeptide GPCR agonists are an emerging class of therapeutics of which a few examples have demonstrated high efficacy in animal models of a variety of diseases. One lanthipeptide GPCR agonist has successfully passed clinical Phase Ia.


id: cord-018401-josb16pi
title: Hierarchical Self-Assembled Peptide Nano-ensembles
author: Kumaraswamy, Priyadharshini
date: 2014-03-01
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123264/
doi: 10.1007/978-3-642-31107-9_23
abstract:
  A variety of peptides can be self-assembled, i.e. self-organized spontaneously, into large and complex hierarchical structures, reproducibly by regulating a range of parameters that can be environment driven, process driven, or peptide driven. These supramolecular peptide aggregates yield different shapes and structures like nanofibers, nanotubes, nanobelts, nanowires, nanotapes, and micelles. These peptide nanostructures represent a category of materials that bridge biotechnology and nanotechnology and are found suitable not only for biomedical applications such as tissue engineering and drug delivery but also in nanoelectronics.


id: cord-022499-7d58f1k3
title: Transmembrane α helices
author: Mall, Sanjay
date: 2004-01-07
txt: ./txt/cord-022499-7d58f1k3.txt
cache: ./cache/cord-022499-7d58f1k3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157917/
doi: 10.1016/s1063-5823(02)52014-7
summary:
  For example, if effects were averaged over three shells of lipids, changes in fatty acyl chain lengths by 4 and 10 carbons from that giving optimal interaction would decrease lipid-protein binding constants by factors of 1.6 and 21, respectively. These results suggest that the effects of charge on the interactions between phospholipids and transmembrane ot helices will often be rather small and will be strongly dependent on the detailed structure of the peptide and its orientation in the membrane. However, there is evidence for the presence of a small number of "special" anionic phospholipids binding to some membrane proteins, acting as "cofactors." An example is provided by cytochrome c oxidase, whose crystal structure shows the presence of a lipid molecule bound between the transmembrane a helices (Iwata et al., 1995) . It could therefore be that matching of the thickness of the lipid bilayer and the transmembrane length of the protein is important in retention in ER, as was suggested for the Golgi complex.

abstract:
  This chapter discusses effects of intrinsic membrane proteins on lipid bilayers and model transmembrane α helices. Incorporation of a protein into a lipid bilayer has significant effects on the properties of the bilayer. The rough surface presented by a protein to the surrounding lipid bilayer tends to produce poor packing unless the lipid fatty acyl chains distort to match the surface of the protein. In a liquid crystalline bilayer the lipid fatty acyl chains are disordered, because the chains undergo extensive wobbling fluctuations. The presence of a rigid protein surface reduces the extent of these motional fluctuations. However, the chains tilt and become conformationally disordered to maximize contact with the rough surface of the protein. The net result is that the presence of a protein leads to decreased order for the chains, with a wide range of chain orientations relative to the bilayer normal, but with reduced extent and rate of motion. Because of the reduced motion, lipids adjacent to membrane proteins are often referred to as being motionally restricted. It is clear that the reasons for the disorder of the bulk lipids and the disorder of the lipids adjacent to the protein are different; for the bulk phospholipids, the disorder is dynamic, whereas, for the boundary lipids the disorder is static.


id: cord-022779-himray6q
title: Abstracts of oral presentations
author: nan
date: 2005-06-10
txt: ./txt/cord-022779-himray6q.txt
cache: ./cache/cord-022779-himray6q.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161772/
doi: 10.1002/bip.20321
abstract: nan
summary:
  Here we present a novel strategy to synthesize proteins through a chemical ligation using unprotected peptide segments. Using short portions (7-11 amino acid) rich in positively charged residues from either human lactoferricin or the MARCKS protein as templates, a panel of 70 peptides each possessing a specific chemical structure was synthesized. Subsequent functionalization of such azide groups via Staudinger or "Click" chemistry should provide a convenient method for linking proteins with a diverse array of probes, biomolecules, surfaces and other materials under mild conditions. Moreover, the advantages of peptide and protein chemical synthesis over recombinant-DNA methods are increasingly being used to provide rapid structure-activity information of complex bioactive peptides, small proteins and functional receptor domains. Thus, these new peptides bear all of the requirements which are necessary for formation of cooperatively interacting helical structures and, furthermore, contain domains for cooperative sheet aggregation as well.


id: cord-022955-vy0qgtll
title: Proteases
author: nan
date: 2005-06-20
txt: ./txt/cord-022955-vy0qgtll.txt
cache: ./cache/cord-022955-vy0qgtll.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164095/
doi: 10.1111/j.1742-4658.2005.4739_4.x
abstract: nan
summary:
  In order to understand the molecular basis of the enzyme-substrate binding mechanism, we employ the synthetic peptide and mass spectrometry-based approaches to investigate the significance of selected amino acid residues that are flanking both sides of the SARS-CoV 3CL pro cleavage site. To contribute to the assignment of a physiological role to genomic-derived peptidases and to make them more accessible for the drug discovery process, we have undertaken a program consisting of mRNA expression profiling, full-length recombinant expression in insect cells, purification and determination of the catalytic activity for the human proteolytic enzymes. This comprehensive analysis of the local backbone properties of SGTI in the free and in the complex form made possible to identify conformational similarities and differences responsible for its efficient binding to the enzyme, and provides a good basis for further studying the structural aspects of protease inhibitor specificity.


id: cord-023200-3caevjvh
title: Membranotropic peptides mediating viral entry
author: Falanga, Annarita
date: 2018-02-13
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167733/
doi: 10.1002/pep2.24040
abstract:
  The means used by enveloped viruses to bypass cellular membranes are well characterized; however, the mechanisms used by non‐enveloped viruses to deliver their genome inside the cell remain unresolved and poorly defined. The discovery of short, membrane interacting, amphipathic or hydrophobic sequences (known as membranotropic peptides) in both enveloped and non‐enveloped viruses suggests that these small peptides are strongly involved in breaching the host membrane and in the delivery of the viral genome into the host cell. Thus, in spite of noticeable differences in entry, this short stretches of membranotropic peptides are probably associated with similar entry‐related events. This review will uncover the intrinsic features of viral membranotropic peptides involved in viral entry of both naked viruses and the ones encircled with a biological membrane with the objective to better elucidate their different functional properties and possible applications in the biomedical field.


id: cord-023208-w99gc5nx
title: Poster Presentation Abstracts
author: nan
date: 2006-09-01
txt: ./txt/cord-023208-w99gc5nx.txt
cache: ./cache/cord-023208-w99gc5nx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167816/
doi: 10.1002/psc.797
abstract: nan
summary:
  In order to develop a synthetic protocol by an automated instrumentation, increasing yield, purity of the crude, and reaction time, a microwave-assisted solid phase peptide synthesis was validated comparing the use of the new generation of Triazine-Based Coupling Reagents (TBCRs) with a series of commonly used ones. Ubiquitinium is a well known mechanism in protein degredation of Eukaryotic cells ,in which many obsolte and corrupted three dimentional structure protein ,become marked by covalent attachment of ubuquitin through a multi-step enzymatic pathway.Ubiquitin is a small ,8.5 kDa peptide of 76 amino acid residues that targets such substrtes for proteolysis in proteasome .Recnt studies showed that an extra cellular ubiquitination process also taking place in the epididymes of humans and other animals marks protein on the surface of the defective sperm .it appears that structurally and functionally defective sperm become surface ubiquitinated by epididymal epithelial cells. This head-to-tailcyclized 14-amino-acid peptide contains one disulfide bridge and a lysine residue (Lys5) present in the P1 position, which is responsible for inhibitor specificity.As was reported by us and other groups, SFTI-1 analogues with one cycle only retain trypsin inhibitory activity.


id: cord-023209-un2ysc2v
title: Poster Presentations
author: nan
date: 2008-10-07
txt: ./txt/cord-023209-un2ysc2v.txt
cache: ./cache/cord-023209-un2ysc2v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167823/
doi: 10.1002/psc.1090
abstract: nan
summary:
  Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds.


id: cord-023225-5quigar4
title: Posters
author: nan
date: 2012-08-21
txt: ./txt/cord-023225-5quigar4.txt
cache: ./cache/cord-023225-5quigar4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167970/
doi: 10.1002/psc.2449
abstract: No abstract is available for this article.
summary:
  To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues.


id: cord-024193-khdvj6t5
title: Peptide Arrays
author: Zhang, Hong
date: 2012-01-17
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193736/
doi: 10.1007/978-3-642-28203-4_7
abstract:
  Despite the concern over the potential loss of structural information as a result of the use of peptides as opposed to proteins as molecular probes, peptide arrays have been implemented in a broad range of applications including antibody screening and epitope mapping, characterization of molecular interactions, and enzymatic activity profiling, and they have become a valuable tool for proteomics research. In this chapter, we first (Sect. 7.1) recapitulate the development of these arrays and highlight a couple of key improvements in the array production and the application in proteomics research. For clinical and biomarker development applications, it is important to measure entities that are directly related to physiological function (and dysfunction). In this respect, the assessment of enzymatic activities is obviously preferable to genotyping, expression profiling, or even measurement of protein amounts. In Sect. 7.2, an original technology based on peptides arrayed onto a porous support allows detailed profiling of kinase activities in a biological sample. The applications described range from kinase characterization to inhibition profiles, detection of off-target effects, and drug response prediction in a clinical setting, allowing rational choice of the drug to be used. Such directly functional approaches will have an important role in the transition to more personalized medicine. Finally, in Sect. 7.3, a recently developed method for “laser printing” of peptide arrays that will make these approaches much more practical is presented.


id: cord-031957-df4luh5v
author: dos Santos-Silva, Carlos André
date: 2020-09-02
txt: ./txt/cord-031957-df4luh5v.txt
cache: ./cache/cord-031957-df4luh5v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476358/
doi: 10.1177/1177932220952739
summary:
  19 Plant AMPs are the central focus of the present review, comprising information on their structural features (at genomic, gene, and protein levels), resources, and bioinformatic tools available, besides the proposition of an annotation routine. 26 Plant AMPs are also classified into families considering protein sequence similarity, cysteine motifs, and distinctive patterns of disulfide bonds, which determine the folding of the tertiary structure. 27, 31 These AMP categories will be detailed in the next sections, together with other groups here considered (Impatienlike, Macadamia [β-barrelins], Puroindoline (PIN), and Thaumatin-like protein [TLP]) and the recently described αhairpinin AMPs. The description includes comments on their structure, pattern for regular expression (REGEX) analysis (when available), functions, tissue-specificity, and scientific data availability. 179 As to the TLP structure, this protein presents characteristic thaumatin signature (PS00316): 180, 181 Most of the TLPs have molecular mass ranging from 21 to 26 kDa, 163 possessing 16 conserved cysteine residues (Supplementary Figure S8) involved in the formation of 8 disulfide bonds, 182 which help in the stability of the molecule, allowing a correct folding even under extreme conditions of temperature and pH.

title:
  Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era

abstract:
  Even before the perception or interaction with pathogens, plants rely on constitutively guardian molecules, often specific to tissue or stage, with further expression after contact with the pathogen. These guardians include small molecules as antimicrobial peptides (AMPs), generally cysteine-rich, functioning to prevent pathogen establishment. Some of these AMPs are shared among eukaryotes (eg, defensins and cyclotides), others are plant specific (eg, snakins), while some are specific to certain plant families (such as heveins). When compared with other organisms, plants tend to present a higher amount of AMP isoforms due to gene duplications or polyploidy, an occurrence possibly also associated with the sessile habit of plants, which prevents them from evading biotic and environmental stresses. Therefore, plants arise as a rich resource for new AMPs. As these molecules are difficult to retrieve from databases using simple sequence alignments, a description of their characteristics and in silico (bioinformatics) approaches used to retrieve them is provided, considering resources and databases available. The possibilities and applications based on tools versus database approaches are considerable and have been so far underestimated.


id: cord-048360-n9sih438
title: Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif
author: Villard, Viviane
date: 2007-07-25
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920550/
doi: 10.1371/journal.pone.0000645
abstract:
  To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.


id: cord-103421-46owvqw8
author: Saunders, Jaclyn K.
date: 2020-05-21
txt: ./txt/cord-103421-46owvqw8.txt
cache: ./cache/cord-103421-46owvqw8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.20.107490
doi: 10.1101/2020.05.20.107490
summary:
  Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). This feature previously existed in METATRYP v 1 for generating peptide redundancy tables within the "Genome" sequencing data category and was used to show the relatively low occurrence of shared peptides across disparate taxa in the open ocean microbiome [1] .

title:
  METATRYP v 2.0: Metaproteomic Least Common Ancestor Analysis for Taxonomic Inference Using Specialized Sequence Assemblies - Standalone Software and Web Servers for Marine Microorganisms and Coronaviruses

abstract:
  We present METATRYP version-2 software that identifies shared peptides across organisms within environmental metaproteomics studies to enable accurate taxonomic attribution of peptides during protein inference. Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Major expansion of the marine database confirms low occurrence of shared tryptic peptides among disparate marine microorganisms, implying tractability for targeted metaproteomics. METATRYP was designed for ocean metaproteomics and has been integrated into the Ocean Protein Portal (https://oceanproteinportal.org); however, it can be readily applied to other domains. We describe the rapid deployment of a coronavirus-specific web portal (https://metatryp-coronavirus.whoi.edu/) to aid in use of proteomics on coronavirus research during the ongoing pandemic. A Coronavirus-focused METATRYP database identified potential SARS-CoV-2 peptide biomarkers and indicated very few shared tryptic peptides between SARS-CoV-2 and other disparate taxa, sharing 0.1% peptides or less (1 peptide) with the Influenza A & B pan-proteomes, establishing that taxonomic specificity is achievable using tryptic peptide-based proteomic diagnostic approaches. Statement of significance When assigning taxonomic attribution in bottom-up metaproteomics, the potential for shared tryptic peptides among organisms in mixed communities should be considered. The software program METATRYP v 2 and associated interactive web portals enables users to identify the frequency of shared tryptic peptides among taxonomic groups and evaluate the occurrence of specific tryptic peptides within complex communities. METATRYP facilitates phyloproteomic studies of taxonomic groups and supports the identification and evaluation of potential metaproteomic biomarkers.


id: cord-103837-iuvigqdx
title: The Human Leukocyte Antigen Class II Immunopeptidome of SARS-CoV-2 Spike Glycoprotein
author: Knierman, Michael D.
date: 2020-11-13
txt: ./txt/cord-103837-iuvigqdx.txt
cache: ./cache/cord-103837-iuvigqdx.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S2211124720314431
doi: 10.1016/j.celrep.2020.108454
summary:
  Mass spectrometry is used to identify 526 unique sequences from SARS-CoV-2 spike glycoprotein extracellular domain in a complex with human leukocyte antigen class II molecules on antigen presenting cells from a panel of healthy donors selected to represent a majority of allele usage from this highly polymorphic molecule. The ability to automate and miniaturize the MAPPs assay enables facile identification of 1000''s of naturally processed and displayed HLA-II peptides from human DCs. Using this approach, we were able J o u r n a l P r e -p r o o f to determine the precise regions and sequences of peptides from SARS-CoV-2 spike glycoprotein ECD derived from a panel of healthy subjects presented for immune surveillance by T-cells. We observed a total of 526 unique peptide sequences contained within 73 clusters distributed across each segment of the SARS-CoV-2 spike glycoprotein ECD presented by human DCs (Figure 2 and Supplemental Table S2 ).

abstract:
  The precise elucidation of the antigen sequences for T-cell immunosurveillance greatly enhances our ability to both understand and modulate humoral responses to viral infection or active immunization. Mass spectrometry is used to identify 526 unique sequences from SARS-CoV-2 spike glycoprotein extracellular domain in a complex with human leukocyte antigen class II molecules on antigen presenting cells from a panel of healthy donors selected to represent a majority of allele usage from this highly polymorphic molecule. The identified sequences span the entire spike protein and several sequences are isolated from a majority of the donors sampled indicating promiscuous binding. Importantly, many peptides derived from the receptor binding domain used for cell entry are identified. This work represents a precise and comprehensive immunopeptidomic investigation with SARS-CoV-2 spike glycoprotein and allows detailed analysis of features which may aid vaccine development to end the current COVID-19 pandemic.


id: cord-252147-bvtchcbt
title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles
author: Domingo-Espín, Joan
date: 2011-11-15
txt: ./txt/cord-252147-bvtchcbt.txt
cache: ./cache/cord-252147-bvtchcbt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/b978-0-12-416020-0.00006-1
doi: 10.1016/b978-0-12-416020-0.00006-1
summary:
  Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer.

abstract:
  The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come.


id: cord-254404-lrsqrc2u
title: Echinoderms provide missing link in the evolution of PrRP/sNPF-type neuropeptide signalling
author: Yañez-Guerra, Luis Alfonso
date: 2020-06-24
txt: ./txt/cord-254404-lrsqrc2u.txt
cache: ./cache/cord-254404-lrsqrc2u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.7554/elife.57640
doi: 10.7554/elife.57640
summary:
  Analysis of transcriptome/genome sequence data revealed loss of NPY/NPF-type signalling, but orthologs of PrRP-type neuropeptides and sNPF/PrRP-type receptors were identified in echinoderms. A more recent finding was the discovery of a family neuropeptide precursor-type proteins in echinoderms that contain a peptide that shares sequence similarity with NPY/NPF-type peptides (Zandawala et al., 2017) . rubens neuropeptide and orthologs from other echinoderms with related peptides in other taxa revealed that they share sequence similarity with both PrRP-type neuropeptides ( Figure 1A ) and with NPY/NPF-type neuropeptides ( Figure 1B) . In echinoderm PrRP-like peptide genes, the exon encoding the neuropeptide is likewise interrupted by an intron but it is located in a different position to the intron that interrupts the coding sequence for NPY/NPF-type peptides. Subsequently, analysis of transcriptomic/genomic sequence data has enabled identification of NPY/NPF-type neuropeptides and their cognate receptors in a variety of invertebrate taxa, revealing a high level of conservation of this signalling system in bilaterian phyla (Zatylny-Gaudin and Favrel, 2014; Fadda et al., 2019) .

abstract:
  Neuropeptide signalling systems comprising peptide ligands and cognate receptors are evolutionarily ancient regulators of physiology and behaviour. However, there are challenges associated with determination of orthology between neuropeptides in different taxa. Orthologs of vertebrate neuropeptide-Y (NPY) known as neuropeptide-F (NPF) have been identified in protostome invertebrates, whilst prolactin-releasing peptide (PrRP) and short neuropeptide-F (sNPF) have been identified as paralogs of NPY/NPF in vertebrates and protostomes, respectively. Here we investigated the occurrence of NPY/NPF/PrRP/sNPF-related signalling systems in a deuterostome invertebrate phylum – the Echinodermata. Analysis of transcriptome/genome sequence data revealed loss of NPY/NPF-type signalling, but orthologs of PrRP-type neuropeptides and sNPF/PrRP-type receptors were identified in echinoderms. Furthermore, experimental studies revealed that the PrRP-type neuropeptide pQDRSKAMQAERTGQLRRLNPRF-NH(2) is a potent ligand for a sNPF/PrRP-type receptor in the starfish Asterias rubens. Our findings indicate that PrRP-type and sNPF-type signalling systems are orthologous and originated as a paralog of NPY/NPF-type signalling in Urbilateria.


id: cord-257494-242k58ll
author: Bastos, Paulo
date: 2017-01-17
txt: ./txt/cord-257494-242k58ll.txt
cache: ./cache/cord-257494-242k58ll.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/med.21435
doi: 10.1002/med.21435
summary:
  1 Human host defense peptides are an intrinsic part of the innate immune system and exhibit a broad activity spectrum against bacteria, fungi, viruses, and parasites While AMPs can be antibacterial (ABPs), antifungal, antiprotist, antiviral, anticancer, antiparasitic, insecticidal, spermicidal, chemotactic, antioxidant, protease inhibitors, or even exhibit wound healing properties (Supporting Information Table S1), their scope of action overlaps considerably and some peptides show activity at several levels (Fig. 2 ). 75 Moreover, when stabilizing disulfide bridges between conserved cysteine residues in human AMPs with β-hairpin or β-sheet conformations are disrupted, the resulting linear peptides still maintain their antimicrobial properties despite losing membranolytic activity. 212, 213 However, it should be noted that the antimicrobial effects of encephalins and their derived peptides result mostly from animal studies and have not been adequately studied in human secretions, despite the high conservation of their sequences across species, which most likely contribute for the similar activity spectrum.

title:
  Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

abstract:
  Antimicrobial peptides (AMPs) are an integral part of the innate immune defense mechanism of many organisms. Due to the alarming increase of resistance to antimicrobial therapeutics, a growing interest in alternative antimicrobial agents has led to the exploitation of AMPs, both synthetic and isolated from natural sources. Thus, many peptide‐based drugs have been the focus of increasing attention by many researchers not only in identifying novel AMPs, but in defining mechanisms of antimicrobial peptide activity as well. Herein, we review the available strategies for the identification of AMPs in human body fluids and their mechanism(s) of action. In addition, an overview of the distribution of AMPs across different human body fluids is provided, as well as its relation with microorganisms and infectious conditions.


id: cord-260392-hj9s5cnu
title: A novel and exploitable antifungal peptide from kale (Brassica alboglabra) seeds
author: Lin, Peng
date: 2008-05-30
url: https://www.ncbi.nlm.nih.gov/pubmed/18597893/
doi: 10.1016/j.peptides.2008.05.020
abstract:
  The aim of this study was to purify and characterize antifungal peptides from kale seeds in view of the paucity of information on antifungal peptides from the family Brassicaceae, and to compare its characteristics with those of published Brassica antifungal peptides. A 5907-Da antifungal peptide was isolated from kale seeds. The isolation procedure comprised affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose and Mono S, and gel filtration on Superdex Peptide. The peptide was adsorbed on the first three chromatographic media. It inhibited mycelial growth in a number of fungal species including Fusarium oxysporum, Helminthosporium maydis, Mycosphaerella arachidicola and Valsa mali, with an IC(50) of 4.3 μM, 2.1 μM, 2.4 μM, and 0.15 μM, respectively and exhibited pronounced thermostability and pH stability. It inhibited proliferation of hepatoma (HepG2) and breast cancer (MCF7) cells with an IC(50) of 2.7 μM and 3.4 μM, and the activity of HIV-1 reverse transcriptase with an IC(50) of 4.9 μM. Its N-terminal sequence differed from those of antifungal proteins which have been reported to date.


id: cord-262253-3ovqhypt
title: The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease
author: Iqbal, Umar H.
date: 2020-07-12
txt: ./txt/cord-262253-3ovqhypt.txt
cache: ./cache/cord-262253-3ovqhypt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32664669/
doi: 10.3390/ijms21144920
summary:
  The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer''s disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer''s disease. Alzheimer''s Disease Aβ amyloid-β AMP antimicrobial peptide APP amyloid precursor proteins BACE1 B-site ABPP cleaving enzyme BBB blood brain barrier CNS central nervous system HSV-1 herpes simplex virus-1 MBP-1 major basic protein-1 NFTS neurofibrillary tangles Protective Effect of Amyloid-beta Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model The Alzheimer''s disease-associated amyloid beta-protein is an antimicrobial peptide Antivirals reduce the formation of key Alzheimer''s disease molecules in cell cultures acutely infected with herpes simplex virus type 1

abstract:
  The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer’s disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. With success in interventions aimed at depleting amyloid-β peptides being limited at best, a greater understanding of the physiological role of amyloid-β peptides is needed. The development of amyloid-β plaques has been determined to occur 10–20 years prior to AD symptom manifestation, hence earlier interventions might be necessary to address presymptomatic AD. Furthermore, recent studies have suggested that amyloid-β peptides may play a role in innate immunity as an antimicrobial peptide. These findings, coupled with the evidence of pathogens such as viruses and bacteria in AD brains, suggests that the buildup of amyloid-β plaques could be a response to the presence of viruses and bacteria. This has led to the foundation of the antimicrobial hypothesis for AD. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer’s disease.


id: cord-262748-v4xue7ha
title: Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine
author: Xu, Yongtao
date: 2015-12-04
url: https://www.ncbi.nlm.nih.gov/pubmed/26636321/
doi: 10.1371/journal.pone.0144171
abstract:
  The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process.


id: cord-269462-7yozebv2
author: Vitiello, Mariateresa
date: 2010-07-02
txt: ./txt/cord-269462-7yozebv2.txt
cache: ./cache/cord-269462-7yozebv2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1159/000317287
doi: 10.1159/000317287
summary:
  METHODS: Fusion peptides of several enveloped viruses belonging to different virus families were prepared by standard 9-fluorenylmethoxycarbonyl polyamine solid-phase synthesis and used to stimulate U937 cells in vitro to analyze the phosphorylation patterns of the signaling pathways (PKC, Src, Akt, and MAPK pathways). Specific ligand-receptor interactions result in activation of signaling pathways; thus, we selected fusion peptides belonging to each of the known viral classes of fusion glycoproteins in order to verify whether during the interaction with the cell surface, they were sufficient to induce phosphorylation of PKC, Src, Akt, and MAPK pathways, activation of nuclear factor (AP-1 and NF-B), and cytokine release (IL-10 and IFN-␤ ). To selectively analyze the regulation of virus-induced AP-1 and NF-B activation, an ELISA-based Trans-Am technology from nuclear lysates of U937 cells stimulated by viral fusion peptides was performed.

title:
  Viral Fusion Peptides Induce Several Signal Transduction Pathway Activations That Are Essential for Interleukin-10 and Beta-Interferon Production

abstract:
  OBJECTIVES: The deciphering of intracellular signaling pathways that are activated by the interaction between viral fusion peptides and cellular membranes are important for the understanding of both viral replication strategies and host defense mechanisms. METHODS: Fusion peptides of several enveloped viruses belonging to different virus families were prepared by standard 9-fluorenylmethoxycarbonyl polyamine solid-phase synthesis and used to stimulate U937 cells in vitro to analyze the phosphorylation patterns of the signaling pathways (PKC, Src, Akt, and MAPK pathways). Immunoprecipitation and Western blotting were carried out by using phosphospecific antibodies. All samples were also assayed for the presence of IL-10 and IFN-β by ELISA and activation of nuclear factors (AP-1 and NF-κB). RESULTS: We have demonstrated that hydrophobic domains of fusion proteins are able to induce several transduction pathways that lead to cytokine (IFN-β and IL-10) production, an event that appears to be dependent on early activation of AP-1 and NF-κB. CONCLUSIONS: The results obtained on the signaling activity of fusion peptides from different viruses enabled us to shed some light on the complex mechanism of viral entry and more precisely we focused on the exact signaling event induced by hydrophobic domains characteristic of fusion peptides interacting with the cell membrane.


id: cord-269756-tid8a464
title: SARS-CoV fusion peptides induce membrane surface ordering and curvature
author: Basso, Luis G. M.
date: 2016-11-28
txt: ./txt/cord-269756-tid8a464.txt
cache: ./cache/cord-269756-tid8a464.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/srep37131
doi: 10.1038/srep37131
summary:
  Although membrane fusion promoted by class I viral glycoproteins, such as SARS-CoV Spike, human immunodeficiency virus (HIV) gp160 or influenza virus hemagglutinin (HA), has been broadly studied in recent years [16] [17] [18] [19] , many aspects of the molecular mechanism behind the virus-host cell membrane fusion remain unknown, including conformational changes of the lipid bilayers during peptide-membrane interactions. In the present study, we investigated the effects of two putative fusion peptides from SARS-CoV S glycoprotein, corresponding to residues 770-788 (SARS FP ) and 873-888 (SARS IFP ) 13, 15, 22, 23 , on the structural dynamics, physicochemical properties, and thermotropic phase behavior of lipid model membranes by differential scanning calorimetry (DSC), continuous wave (CW) and pulsed electron spin resonance (ESR) along with nonlinear least-squares (NLLS) spectral fitting 24 .

abstract:
  Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.


id: cord-273107-xc61osdx
author: Qureshi, Abid
date: 2014-01-01
url: https://doi.org/10.1093/nar/gkt1191
doi: 10.1093/nar/gkt1191
title:
  AVPdb: a database of experimentally validated antiviral peptides targeting medically important viruses

abstract:
  Antiviral peptides (AVPs) have exhibited huge potential in inhibiting viruses by targeting various stages of their life cycle. Therefore, we have developed AVPdb, available online at http://crdd.osdd.net/servers/avpdb, to provide a dedicated resource of experimentally verified AVPs targeting over 60 medically important viruses including Influenza, HCV, HSV, RSV, HBV, DENV, SARS, etc. However, we have separately provided HIV inhibiting peptides in ‘HIPdb’. AVPdb contains detailed information of 2683 peptides, including 624 modified peptides experimentally tested for antiviral activity. In modified peptides a chemical moiety is attached for increasing their efficacy and stability. Detailed information include: peptide sequence, length, source, virus targeted, virus family, cell line used, efficacy (qualitative/quantitative), target step/protein, assay used in determining the efficacy and PubMed reference. The database also furnishes physicochemical properties and predicted structure for each peptide. We have provided user-friendly browsing and search facility along with other analysis tools to help the users. Entering of many synthetic peptide-based drugs in various stages of clinical trials reiterate the importance for the AVP resources. AVPdb is anticipated to cater to the needs of scientific community working for the development of antiviral therapeutics.


id: cord-274101-vm9nh8lc
author: Perez Espitia, Paula Judith
date: 2012-02-29
txt: ./txt/cord-274101-vm9nh8lc.txt
cache: ./cache/cord-274101-vm9nh8lc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32368201/
doi: 10.1111/j.1541-4337.2011.00179.x
summary:
  The separation occurs because of highly specific biochemical interactions between the peptide and the ligand Used when a high degree of specificity is required, for example, isolation of a target protein present in low concentration in a biological fluid or a cell extract Capillary electrophoresis Based on the migration of the peptide according to its charge in solution, depending on the application of an electric field. Peptides have shown various bioproperties, among them antimicrobial activity, leading to the application of these compounds in the food preservation area by either direct addition or incorporation into packaging materials (Table 8) . Active packaging materials incorporated with antimicrobial peptides have shown effectiveness in inhibiting pathogenic microorganisms, an improvement in food safety. Several studies have indicated significant changes in mechanical properties and surface morphology of the films incorporated with antimicrobial peptides.

title:
  Bioactive Peptides: Synthesis, Properties, and Applications in the Packaging and Preservation of Food

abstract:
  Abstract: Bioactive peptides are protein fragments which have a positive impact on the functions and conditions of living beings. Peptides have shown several useful properties for human health, including antimicrobial, antifungal, antiviral, and antitumor activities. These compounds are produced by almost all species of life. However, they are produced in limited quantities in nature. As a result, researchers have tried to synthesize bioactive peptides to study their properties and applications in various areas. Among their applications in food preservation, peptides have been incorporated into packaging materials. This review begins with a brief description of the methods used for the synthesis, purification, and characterization of peptides. Also, the main bioproperties and mechanisms of action of peptides are discussed. Finally, some applications of peptides are presented, especially their use in active packaging, their effects on the polymeric matrix, and peptide migration.


id: cord-277716-6gsmkmk5
title: Design and optimization of peptide nanoparticles
author: Doll, Tais A. P. F.
date: 2015-10-24
txt: ./txt/cord-277716-6gsmkmk5.txt
cache: ./cache/cord-277716-6gsmkmk5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26498651/
doi: 10.1186/s12951-015-0119-z
summary:
  RESULTS: Here, we were studying in vitro and in silico the effect of the chain length and of point mutations near the linker region between the pentamer and the trimer on the self-assembly of the SAPNs. 60 identical peptide chains co-assemble to form a spherical nanoparticle displaying icosahedral symmetry. All these different mutants along with the initial parent peptide (Fig. 3) were studied by molecular dynamics (MD) simulations using the program CHARMM 36b1 in an attempt to further optimize the linker region and find the best peptide building block for the SAPNs. From the linker constitution study it was found that a malaria nanoparticle vaccine construct self-assembled into almost spherical nanoparticles [21] . Based on our construct design and the biophysical results of the 2.5HR we ran a series of molecular dynamics simulations on the eleven short versions of 2.5HR including only five helical turns (i.e. 2.5 heptad repeats) around the linker region of the nanoparticle peptide (Figs.

abstract:
  BACKGROUND: Various supra-molecular structures form by self-assembly of proteins in a symmetric fashion. Examples of such structures are viruses, some bacterial micro-compartments and eukaryotic vaults. Peptide/protein-based nanoparticles are emerging in synthetic biology for a variety of biomedical applications, mainly as drug targeting and delivery systems or as vaccines. Our self-assembling peptide nanoparticles (SAPNs) are formed by a single peptide chain that consists of two helical coiled-coil segments connected by a short linker region. One helix is forming a pentameric coiled coil while the other is forming a trimeric coiled coil. RESULTS: Here, we were studying in vitro and in silico the effect of the chain length and of point mutations near the linker region between the pentamer and the trimer on the self-assembly of the SAPNs. 60 identical peptide chains co-assemble to form a spherical nanoparticle displaying icosahedral symmetry. We have stepwise reduced the size of the protein chain to a minimal chain length of 36 amino acids. We first used biochemical and biophysical methods on the longer constructs followed by molecular dynamics simulations to study eleven different smaller peptide constructs. We have identified one peptide that shows the most promising mini-nanoparticle model in silico. CONCLUSIONS: An approach of in silico modeling combined with in vitro testing and verification yielded promising peptide designs: at a minimal chain length of only 36 amino acids they were able to self-assemble into proper nanoparticles. This is important since the production cost increases more than linearly with chain length. Also the size of the nanoparticles is significantly smaller than 20 nm, thus reducing the immunogenicity of the particles, which in turn may allow to use the SAPNs as drug delivery systems without the risk of an anaphylactic shock. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-015-0119-z) contains supplementary material, which is available to authorized users.


id: cord-280383-hi7z3nob
title: SAROTUP: Scanner and Reporter of Target-Unrelated Peptides
author: Huang, Jian
date: 2010-03-21
txt: ./txt/cord-280383-hi7z3nob.txt
cache: ./cache/cord-280383-hi7z3nob.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20339521/
doi: 10.1155/2010/101932
summary:
  In this study, we present SAROTUP, a free web tool for scanning, reporting and excluding possible target-unrelated peptides from real mimotopes. There are now quite a few programs for mimotope based epitope mapping, none of them, however, has a procedure to scan, report and exclude target-unrelated peptides [15] [16] [17] [18] [19] [20] [21] [22] [23] . It is capable of finding, reporting, and precluding possible target-unrelated peptides, which is very helpful for the development of mimotope-based diagnostics, therapeutics, and vaccines. Scott reviewed a collection of target-unrelated peptides recovered in the screening of phage-displayed random peptide libraries with antibodies [12] . Although SAROTUP looks a little bit Table 2 , the first test data set has 11 panels of peptides acquired from phage display libraries screened with 8 targets. Furthermore, SAROTUP will not only benefit the mimotope-based epitope mapping, but also the development of new diagnostics, therapeutics, and vaccines.

abstract:
  As epitope mimics, mimotopes have been widely utilized in the study of epitope prediction and the development of new diagnostics, therapeutics, and vaccines. Screening the random peptide libraries constructed with phage display or any other surface display technologies provides an efficient and convenient approach to acquire mimotopes. However, target-unrelated peptides creep into mimotopes from time to time through binding to contaminants or other components of the screening system. In this study, we present SAROTUP, a free web tool for scanning, reporting and excluding possible target-unrelated peptides from real mimotopes. Preliminary tests show that SAROTUP is efficient and capable of improving the accuracy of mimotope-based epitope mapping. It is also helpful for the development of mimotope-based diagnostics, therapeutics, and vaccines.


id: cord-284523-lknyehsa
title: Antiviral activity of animal venom peptides and related compounds
author: da Mata, Élida Cleyse Gomes
date: 2017-01-06
url: https://www.ncbi.nlm.nih.gov/pubmed/28074089/
doi: 10.1186/s40409-016-0089-0
abstract:
  Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.


id: cord-284690-ogu1gmcb
author: da Cunha, Nicolau B.
date: 2016-11-23
txt: ./txt/cord-284690-ogu1gmcb.txt
cache: ./cache/cord-284690-ogu1gmcb.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1359644616304135
doi: 10.1016/j.drudis.2016.10.017
summary:
  The use of viral vectors based on the tobacco mosaic virus (TMV) and potato virus X (PVX) for cloning and massively expressing AMP genes in Nicotiana benthamiana appears to be an interesting new approach to considerably enhance recombinant peptide production before structural and functional characterization. However, frequent gene silencing at the transcriptional level and instability of genes cloned in vectors for stable or transient expression remain major challenges limiting the efficient production of AMPs. Another persistent issue is the poor quality of the peptides endogenously synthesized in bacteria, yeast, and plants, particularly resulting from undesirable post-translational modifications [2, 33] . Some drawbacks presented by plant expression systems are solved by the CRISPR system, a revolutionary genome-editing technology that presents myriad possibilities for genetic manipulation at the genomic level and provides unprecedented tools (CRISPRi and CRISPRa) to precisely control gene expression and the structural modification of AMPs. Despite its current minor limitations (e.g. off-target effects), CRISPR could have a key role in the future development of clinical drugs as biotechnological antiinfective agents, including the rational biosynthesis of next-generation antimicrobials.

title:
  The next generation of antimicrobial peptides (AMPs) as molecular therapeutic tools for the treatment of diseases with social and economic impacts

abstract:
  Anti-infective drugs have had a key role in the contemporary world, contributing to dramatically decrease mortality rates caused by infectious diseases worldwide. Antimicrobial peptides (AMPs) are multifunctional effectors of the innate immune system of mucosal surfaces and present antimicrobial activity against a range of pathogenic viruses, bacteria, and fungi. However, the discovery and development of new antibacterial drugs is a crucial step to overcome the great challenge posed by the emergence of antibiotic resistance. In this review, we outline recent advances in the development of novel AMPs with improved antimicrobial activities that were achieved through characteristic structural design. In addition, we describe recent progress made to overcome some of the major limitations that have hindered peptide biosynthesis.


id: cord-285443-9y2kkmby
title: Cholesterol‐conjugated peptide antivirals: a path to a rapid response to emerging viral diseases
author: Pessi, Antonello
date: 2014-10-20
txt: ./txt/cord-285443-9y2kkmby.txt
cache: ./cache/cord-285443-9y2kkmby.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25331523/
doi: 10.1002/psc.2706
summary:
  The combination of bioinformatic lead identification and potency/pharmacokinetics improvement provided by cholesterol conjugation may form the basis for a rapid response strategy, where development of an emergency cholesterol‐conjugated therapeutic would immediately follow the availability of the genetic information of a new enveloped virus. For example, although the entry of herpes viruses (featuring a class III fusion protein) is a complex process, not yet fully clarified, in which multiple glycoproteins are involved, several laboratories have reported that peptides derived from the HR regions of gB and gH of herpes simplex virus type 1, bovine herpes virus type 1, and human cytomegalovirus are able to inhibit infection [103] . Given the ubiquitous importance of cholesterol-rich lipid rafts in viral fusion, it is expected that cholesterol conjugation may enhance the antiviral potency also for peptides derived from class II and III fusion proteins. Antiviral activity of membrane fusion inhibitors that target gp40 of the feline immunodeficiency virus envelope protein

abstract:
  While it is now possible to identify and genetically fingerprint the causative agents of emerging viral diseases, often with extraordinary speed, suitable therapies cannot be developed with equivalent speed, because drug discovery requires information that goes beyond knowledge of the viral genome. Peptides, however, may represent a special opportunity. For all enveloped viruses, fusion between the viral and the target cell membrane is an obligatory step of the life cycle. Class I fusion proteins harbor regions with a repeating pattern of amino acids, the heptad repeats (HRs), that play a key role in fusion, and HR‐derived peptides such as enfuvirtide, in clinical use for HIV, can block the process. Because of their characteristic sequence pattern, HRs are easily identified in the genome by means of computer programs, providing the sequence of candidate peptide inhibitors directly from genomic information. Moreover, a simple chemical modification, the attachment of a cholesterol group, can dramatically increase the antiviral potency of HR‐derived inhibitors and simultaneously improve their pharmacokinetics. Further enhancement can be provided by dimerization of the cholesterol‐conjugated peptide. The examples reported so far include inhibitors of retroviruses, paramyxoviruses, orthomyxoviruses, henipaviruses, coronaviruses, and filoviruses. For some of these viruses, in vivo efficacy has been demonstrated in suitable animal models. The combination of bioinformatic lead identification and potency/pharmacokinetics improvement provided by cholesterol conjugation may form the basis for a rapid response strategy, where development of an emergency cholesterol‐conjugated therapeutic would immediately follow the availability of the genetic information of a new enveloped virus. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.


id: cord-287123-ldkuwcc7
title: The Formyl Peptide Receptors: Diversity of Ligands and Mechanism for Recognition
author: He, Hui-Qiong
date: 2017-03-13
txt: ./txt/cord-287123-ldkuwcc7.txt
cache: ./cache/cord-287123-ldkuwcc7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules22030455
doi: 10.3390/molecules22030455
summary:
  The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. N-formylated peptides constitute the most commonly studied class of FPR agonists that trigger a variety of biological activities in myeloid cells, such as chemokinesis, chemotaxis, calcium flux, cytokine production and superoxide anion generation. Through binding with the high affinity receptor FPR1, fMLF and other N-formylated peptides serve as potent chemoattractants, which also include activated complements (C5a, C3a) and chemokines, in recruiting and guiding leukocytes to the site of bacterial infection and to damaged tissues. As the first identified endogenous peptide agonist for FPR [56] , documented studies have shown that it exerts pro-inflammatory activities through FPR2 in phagocytes, epithelial cells and T lymphocytes, including stimulating production of inflammatory mediators and enhancing the expression of cytokine receptors [109] [110] [111] [112] [113] .

abstract:
  The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. In recent years, the cellular distribution and biological functions of FPRs have expanded to include additional roles in homeostasis of organ functions and modulation of inflammation. In a prototype, FPRs recognize peptides containing N-formylated methionine such as those produced in bacteria and mitochondria, thereby serving as pattern recognition receptors. The repertoire of FPR ligands, however, has expanded rapidly to include not only N-formyl peptides from microbes but also non-formyl peptides of microbial and host origins, synthetic small molecules and an eicosanoid. How these chemically diverse ligands are recognized by the three human FPRs (FPR1, FPR2 and FPR3) and their murine equivalents is largely unclear. In the absence of crystal structures for the FPRs, site-directed mutagenesis, computer-aided ligand docking and structural simulation have led to the identification of amino acids within FPR1 and FPR2 that interact with several formyl peptides. This review article summarizes the progress made in the understanding of FPR ligand diversity as well as ligand recognition mechanisms used by these receptors.


id: cord-289161-d7shmb2o
title: Antimicrobial peptides from scorpion venoms
author: Harrison, Patrick L.
date: 2014-09-15
txt: ./txt/cord-289161-d7shmb2o.txt
cache: ./cache/cord-289161-d7shmb2o.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0041010114001688
doi: 10.1016/j.toxicon.2014.06.006
summary:
  This review aims to provide an examination of AMPs from scorpion venom (Table 1; Fig. 1 ), with discussions on structure, biological activity and proposed mechanisms of action, together with a final discussion of recent and future strategies for mining new bioactive molecules. This substitution creates a more flexible region while retaining the essential amphipathic nature of Pin 2 which is more in tune with the dual helical structure of Corzo, Nakajima and colleagues have subsequently demonstrated that the haemolytic activity of Pin1, Pin2 and other cationic amphipathic peptides (e.g. IsCt1, see Section 3.3) depends on the animal species studied (guinea pig > pig > sheep) and this is turn is related to the phosphatidylcholine:sphingomyelin ratio in the different erythrocyte membranes (Belokoneva et al., 2003) . CD spectral analysis of synthetic meucin-24 (2.8 kDa, 24 amino acids) showed a disordered conformation in water; however a-helical formation increased in 50% TFE and NMR spectra revealed an a-helical structure between residues 4e20 and random coil regions at the N-and C-terminals (Gao et al., 2010) .

abstract:
  The need for new antimicrobial agents is becoming one of the most urgent requirements in modern medicine. The venoms of many different species are rich sources of biologically active components and various therapeutic agents have been characterized including antimicrobial peptides (AMPs). Due to their potent activity, low resistance rates and unique mode of action, AMPs have recently received much attention. This review focuses on AMPs from the venoms of scorpions and examines all classes of AMPs found to date. It gives details of their biological activities with reference to peptide structure. The review examines the mechanism of action of AMPs and with this information, suggests possible mechanisms of action of less well characterised peptides. Finally, the review examines current and future trends of scorpion AMP research, by discussing recent successes obtained through proteomic and transcriptomic approaches.


id: cord-291534-c6cjxq07
title: Cationic Host Defence Peptides: Potential as Antiviral Therapeutics
author: Gwyer Findlay, Emily
date: 2013-05-07
url: https://doi.org/10.1007/s40259-013-0039-0
doi: 10.1007/s40259-013-0039-0
abstract:
  There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics.


id: cord-293072-giakcaki
author: Xu, Wan-Xiang
date: 2017-10-12
url: https://doi.org/10.1371/journal.pone.0186097
doi: 10.1371/journal.pone.0186097
title:
  A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping

abstract:
  There is a need to develop better methods for epitope mapping and/or identification of antibody-recognizing motifs. Here, we describe improved biosynthetic peptide (BSP) method using a newly developed plasmid pXXGST-3 as vector, which has a viral E7 gene in the cloning sites of pXXGST-1. It is crucial to employ pXXGST-3 instead of pXXGST-1, since it makes use of the BSP method simpler and easier to perform, and more cost-effective for epitope mapping. These merits are embodied in two aspects: i) convenient recovery of double enzyme-digested product due to the existence of 315 bp inserted between BamH I and Sal I sites, and thus greatly reducing the production of self-ligation clones, and ii) no longer requiring control protein when screening recombinant (r-) clones expressing 8/18mer peptides by running polyacrylamide gel electrophoresis. The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. This improved GST188-BSP method provides a powerful alternative tool for epitope mapping.


id: cord-295207-0p6x4lwx
title: Peptide inhibition of human cytomegalovirus infection
author: Melnik, Lilia I
date: 2011-02-22
txt: ./txt/cord-295207-0p6x4lwx.txt
cache: ./cache/cord-295207-0p6x4lwx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1743-422x-8-76
doi: 10.1186/1743-422x-8-76
summary:
  The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Previous studies have suggested that synthetic peptides corresponding to or overlapping with sequences in viral fusion proteins that have positive WWIHS scores can sometimes serve as viral entry inhibitors [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] . For example, Enfurvitide (Fuzeon) is a 36-amino acid peptide that overlaps with a WWIHS score-positive sequence in the transmembrane protein (TM) of HIV-1, and prevents viral fusion and entry of the virus. These results suggest that the HCMV inhibitory peptides identified here may serve as Figure 2 Determination of regions within gB that display a high propensity to interact with the lipid surface of cell membranes by using Wimley-White Interfacial Hydrophobicity Scale (WWIHS).

abstract:
  BACKGROUND: Human cytomegalovirus (HCMV) is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV)- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. RESULTS: Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF) were infected with the Towne-GFP strain of HCMV (0.5 MOI), preincubated with peptides at a range of concentrations (78 nm to 100 μM), and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 μM and 50 μM, respectively, and 60% at a concentration of 2.5 μM. While peptides 264-291 and 297-315, individually failed to inhibit viral infection, when combined, they showed 67% inhibition of HCMV infection at a concentration of 0.125 μM each. CONCLUSIONS: Peptides designed to target putative fusogenic domains of gB provide a basis for the development of novel therapeutics that prevent HCMV infection.


id: cord-298019-gf2asni1
title: gH625: A milestone in understanding the many roles of membranotropic peptides
author: Galdiero, Stefania
date: 2014-10-12
txt: ./txt/cord-298019-gf2asni1.txt
cache: ./cache/cord-298019-gf2asni1.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0005273614003411
doi: 10.1016/j.bbamem.2014.10.006
summary:
  While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. Peptides with a propensity for membrane binding can also interfere with enveloped virus entry by direct physical interaction with the hydrophobic surfaces present on cell membranes and/or fusion proteins. Since not all membranotropic peptides are able to cross the membrane bilayer, it is essential to identify structural characteristics of hydrophobic peptides know to enter the cell membrane to highlight any feature that is involved in the penetration which may help in the design of novel delivery tools. Dendrimer functionalization with a membrane-interacting domain of herpes simplex virus type 1: towards intracellular delivery

abstract:
  Here, we review the current knowledge about viral derived membranotropic peptides, and we discuss how they may be used for many therapeutic applications. While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. The peptide gH625 has been extensively used for all these purposes and provides a significant contribution to the field. We describe the roles of this sequence in order to close the gap between the many functions that are now emerging for membranotropic peptides.


id: cord-300189-gsp1dozg
author: Franci, Gianluigi
date: 2017-02-14
txt: ./txt/cord-300189-gsp1dozg.txt
cache: ./cache/cord-300189-gsp1dozg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/psc.2979
doi: 10.1002/psc.2979
summary:
  To date, few peptide molecules outside the well-known inhibitory regions of Class 1 viral fusion proteins, the heptad repeats, should be as fusion; therefore, a brute force approach to the identification of peptide entry inhibitors may help in the dissection of HSV-1 glycoproteins domains. Previous works using a physico-chemical algorithm, the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), in combination with other structural data allowed us to predict regions in gH potentially involved in membrane interactions during the entry and fusion process, and some of them were found to possess HSV antiviral activity in dose-dependent inhibition assays [66] . [76] used a phage display methodology to identify a peptide (named P1) to inhibit West Nile virus (WNV) infectivity, possibly by binding to the envelope glycoprotein (E protein) necessary for membrane fusion. Substitution of herpes simplex virus 1 entry glycoproteins with those of saimiriine herpesvirus 1 reveals a gD-gH/gL functional interaction and a region within the gD profusion domain that is critical for fusion

title:
  Infectivity inhibition by overlapping synthetic peptides derived from the gH/gL heterodimer of herpes simplex virus type 1

abstract:
  Herpes simplex virus (HSV) is a human pathogen that infects epithelial cells. The cutaneous lesions, caused by the virus, spread to the nervous system creating several complications. Fusion of host membranes with the viral envelope is mandatory and mediated by a group of glycoproteins conserved in all Herpesviridae subfamilies, such as the glycoproteins B (gB), H (gH), L (gL) and D (gD). We investigated the inhibitory activity mediated by synthetic overlapping peptides spanning the entire ectodomains of gH and gL glycoproteins. We have performed a brute analysis of the complete gH/gL heterodimer in order to explore the inhibitory activity of peptides modelled on these glycoproteins against HSV‐1 infection. Twenty‐four of the gH peptides at a concentration of 150 μM reached the 50% of inhibition cut‐off. Interestingly, they are mainly located in the gH carboxy‐terminal domain. None of the gL peptides had a clear inhibiting effect. No peptide toxicity was observed by lactate dehydrogenase assay at the concentrations used in our experimental conditions. HSV‐1 therapy is based on acyclovir treatment, but some resistant strains are emerging. In this scenario, innovative approaches for HSV‐1 treatment are necessary. Our data support the direct involvement of the described domains in the process of virus penetration; therefore, these results are of relevance to the potential development of novel therapeutic compounds to prevent HSV‐1 infections. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


id: cord-305755-6jup93v4
author: Gouveia, Duarte
date: 2020-07-22
url: https://www.ncbi.nlm.nih.gov/pubmed/32697082/
doi: 10.1021/acs.jproteome.0c00535
title:
  Proteotyping SARS-CoV-2 Virus from Nasopharyngeal Swabs: A Proof-of-Concept Focused on a 3 Min Mass Spectrometry Window

abstract:
  [Image: see text] Rapid but yet sensitive, specific, and high-throughput detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples is key to diagnose infected people and to better control the spread of the virus. Alternative methodologies to PCR and immunodiagnostics that would not require specific reagents are worthy to investigate not only for fighting the COVID-19 pandemic but also to detect other emergent pathogenic threats. Here, we propose the use of tandem mass spectrometry to detect SARS-CoV-2 marker peptides in nasopharyngeal swabs. We documented that the signal from the microbiota present in such samples is low and can be overlooked when interpreting shotgun proteomic data acquired on a restricted window of the peptidome landscape. In this proof-of-concept study, simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC–MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. We argue that peptides ADETQALPQR and GFYAQGSR from the nucleocapsid protein are of utmost interest as their signal is intense and their elution can be obtained within a 3 min window in the tested conditions. These results pave the way for the development of time-efficient viral diagnostic tests based on mass spectrometry.


id: cord-307909-7vbxyns0
author: Ronda, Luca
date: 2020-09-02
url: https://www.ncbi.nlm.nih.gov/pubmed/32887407/
doi: 10.3390/s20174977
title:
  Rational Design of a User-Friendly Aptamer/Peptide-Based Device for the Detection of Staphylococcus aureus

abstract:
  The urgent need to develop a detection system for Staphylococcus aureus, one of the most common causes of infection, is prompting research towards novel approaches and devices, with a particular focus on point-of-care analysis. Biosensors are promising systems to achieve this aim. We coupled the selectivity and affinity of aptamers, short nucleic acids sequences able to recognize specific epitopes on bacterial surface, immobilized at high density on a nanostructured zirconium dioxide surface, with the rational design of specifically interacting fluorescent peptides to assemble an easy-to-use detection device. We show that the displacement of fluorescent peptides upon the competitive binding of S. aureus to immobilized aptamers can be detected and quantified through fluorescence loss. This approach could be also applied to the detection of other bacterial species once aptamers interacting with specific antigens will be identified, allowing the development of a platform for easy detection of a pathogen without requiring access to a healthcare environment.


id: cord-314604-w61sqy17
title: Modulation of Coiled-Coil Binding Strength and Fusogenicity through Peptide Stapling
author: Crone, Niek S. A.
date: 2020-02-14
url: https://www.ncbi.nlm.nih.gov/pubmed/32058706/
doi: 10.1021/acs.bioconjchem.0c00009
abstract:
  [Image: see text] Peptide stapling is a technique which has been widely employed to constrain the conformation of peptides. One of the effects of such a constraint can be to modulate the interaction of the peptide with a binding partner. Here, a cysteine bis-alkylation stapling technique was applied to generate structurally isomeric peptide variants of a heterodimeric coiled-coil forming peptide. These stapled variants differed in the position and size of the formed macrocycle. C-terminal stapling showed the most significant changes in peptide structure and stability, with calorimetric binding analysis showing a significant reduction of binding entropy for stapled variants. This entropy reduction was dependent on cross-linker size and was accompanied by a change in binding enthalpy, illustrating the effects of preorganization. The stapled peptide, along with its binding partner, were subsequently employed as fusogens in a liposome model system. An increase in both lipid- and content-mixing was observed for one of the stapled peptide variants: this increased fusogenicity was attributed to increased coiled-coil binding but not to membrane affinity, an interaction theorized to be a primary driving force in this fusion system.


id: cord-315115-f61xcnuw
author: Wang, Guangshun
date: 2020-08-07
txt: ./txt/cord-315115-f61xcnuw.txt
cache: ./cache/cord-315115-f61xcnuw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32784626/
doi: 10.3390/antibiotics9080491
summary:
  title: Bioinformatic Analysis of 1000 Amphibian Antimicrobial Peptides Uncovers Multiple Length-Dependent Correlations for Peptide Design and Prediction For this study, we found 1015 frog antimicrobial peptides in the APD3, ranging from 5 to 63 amino acids (an average length of 24) [78] . Antibiotics 2020, 9, x FOR PEER REVIEW 4 of 26 For this study, we found 1015 frog antimicrobial peptides in the APD3, ranging from 5 to 63 amino acids (an average length of 24) [78] . These numbers can be regarded as minimal since many predicted/isolated AMPs without Antibiotics 2020, 9, 491 5 of 26 antimicrobial activity data or those tested to be inactive (MIC > 100 µM) are not included in our analysis. This study focuses on amphibian peptides with demonstrated antimicrobial activity collected in the APD database. Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin

title:
  Bioinformatic Analysis of 1000 Amphibian Antimicrobial Peptides Uncovers Multiple Length-Dependent Correlations for Peptide Design and Prediction

abstract:
  Amphibians are widely distributed on different continents, except for the polar regions. They are important sources for the isolation, purification and characterization of natural compounds, including peptides with various functions. Innate immune antimicrobial peptides (AMPs) play a critical role in warding off invading pathogens, such as bacteria, fungi, parasites, and viruses. They may also have other biological functions such as endotoxin neutralization, chemotaxis, anti-inflammation, and wound healing. This article documents a bioinformatic analysis of over 1000 amphibian antimicrobial peptides registered in the Antimicrobial Peptide Database (APD) in the past 18 years. These anuran peptides were discovered in Africa, Asia, Australia, Europe, and America from 1985 to 2019. Genomic and peptidomic studies accelerated the discovery pace and underscored the necessity in establishing criteria for peptide entry into the APD. A total of 99.9% of the anuran antimicrobial peptides are less than 50 amino acids with an average length of 24 and a net charge of +2.5. Interestingly, the various amphibian peptide families (e.g., temporins, brevinins, esculentins) can be connected through multiple length-dependent relationships. With an increase in length, peptide net charge increases, while the hydrophobic content decreases. In addition, glycine, leucine, lysine, and proline all show linear correlations with peptide length. These correlations improve our understanding of amphibian peptides and may be useful for prediction and design of new linear peptides with potential applications in treating infectious diseases, cancer and diabetes.


id: cord-316474-407bthqj
title: Bioinformatics Resources and Tools for Phage Display
author: Huang, Jian
date: 2011-01-18
txt: ./txt/cord-316474-407bthqj.txt
cache: ./cache/cord-316474-407bthqj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules16010694
doi: 10.3390/molecules16010694
summary:
  Since the pioneering work described above, phage display technology has further been developed and improved by scientists from various fields, and its applications has extended from epitope mapping to antibody engineering and organ targeting [2] [3] [4] [5] . Mimotopes can now be obtained in a relatively cheap, efficient and convenient way, i.e. screening phage-displayed random peptide libraries with a given target. In this review, we will summarize the special databases, algorithms, programs, web servers and their applications in the phage display area, focusing on the tools for mimotope-based epitope mapping. With these tools, phage display technology has shown its power in exploring the interactions between proteins, peptides and small molecule ligands. Powered by special computational tools developed for phage display technology, not only linear epitope but also conformational epitope formed by discontinuous residues brought into spatial proximity by protein folding can be mapped reasonably.

abstract:
  Databases and computational tools for mimotopes have been an important part of phage display study. Five special databases and eighteen algorithms, programs and web servers and their applications are reviewed in this paper. Although these bioinformatics resources have been widely used to exclude target-unrelated peptides, characterize small molecules-protein interactions and map protein-protein interactions, a lot of problems are still waiting to be solved. With the improvement of these tools, they are expected to serve the phage display community better.


id: cord-316792-89f8g0m8
title: Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery
author: Herzig, Volker
date: 2020-06-12
txt: ./txt/cord-316792-89f8g0m8.txt
cache: ./cache/cord-316792-89f8g0m8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32535105/
doi: 10.1016/j.bcp.2020.114096
summary:
  Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. Since many venoms and toxins exert these biological effects through actions on cell membranes, receptors and ion channels, high-throughput techniques assessing changes in cellular signalling have proven particularly insightful. Spider-venom peptides have been crucial for uncovering the key role of ASICs in stroke-induced brain damage, and validating these channels as a target for neuroprotective drugs [134] [135] [136] [137] .

abstract:
  Venomous animals have evolved toxins that interfere with specific components of their victim’s core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.


id: cord-320497-e5pb83mj
author: Zunszain, Patricia A.
date: 2010-01-15
url: https://doi.org/10.1016/j.jmb.2009.10.048
doi: 10.1016/j.jmb.2009.10.048
title:
  Insights into Cleavage Specificity from the Crystal Structure of Foot-and-Mouth Disease Virus 3C Protease Complexed with a Peptide Substrate

abstract:
  Abstract Picornavirus replication is critically dependent on the correct processing of a polyprotein precursor by 3C protease(s) (3Cpro) at multiple specific sites with related but non-identical sequences. To investigate the structural basis of its cleavage specificity, we performed the first crystallographic structural analysis of non-covalent complexes of a picornavirus 3Cpro with peptide substrates. The X-ray crystal structure of the foot-and-mouth disease virus 3Cpro, mutated to replace the catalytic Cys by Ala and bound to a peptide (APAKQ|LLNFD) corresponding to the P5–P5′ region of the VP1-2A cleavage junction in the viral polyprotein, was determined up to 2.5 Å resolution. Comparison with free enzyme reveals significant conformational changes in 3Cpro on substrate binding that lead to the formation of an extended interface of contact primarily involving the P4–P2′ positions of the peptide. Strikingly, the deep S1′ specificity pocket needed to accommodate P1′-Leu only forms when the peptide binds. Substrate specificity was investigated using peptide cleavage assays to show the impact of amino acid substitutions within the P5–P4′ region of synthetic substrates. The structure of the enzyme–peptide complex explains the marked substrate preferences for particular P4, P2 and P1 residue types, as well as the relative promiscuity at P3 and on the P′ side of the scissile bond. Furthermore, crystallographic analysis of the complex with a modified VP1-2A peptide (APAKE|LLNFD) containing a Gln-to-Glu substitution reveals an identical mode of peptide binding and explains the ability of foot-and-mouth disease virus 3Cpro to cleave sequences containing either P1-Gln or P1-Glu. Structure-based mutagenesis was used to probe interactions within the S1′ specificity pocket and to provide direct evidence of the important contribution made by Asp84 of the Cys-His-Asp catalytic triad to proteolytic activity. Our results provide a new level of detail in our understanding of the structural basis of polyprotein cleavage by 3Cpro.


id: cord-320693-de1lmzl1
title: Antiviral activity of Piscidin 1 against pseudorabies virus both in vitro and in vivo
author: Hu, Han
date: 2019-07-31
url: https://doi.org/10.1186/s12985-019-1199-4
doi: 10.1186/s12985-019-1199-4
abstract:
  BACKGROUND: Swine-origin virus infection spreading widely could cause significant economic loss to porcine industry. Novel antiviral agents need to be developed to control this situation. METHODS: In this study, we evaluated the activities of five broad-spectrum antimicrobial peptides (AMPs) against several important swine-origin pathogenic viruses by TCID(50) assay. Plaque reduction assay and cell apoptosis assay were also used to test the activity of the peptides. Protection effect of piscidin against pseudorabies virus (PRV) was also examined in mouse model. RESULTS: Piscidin (piscidin 1), caerin (caerin 1.1) and maculatin (maculatin 1.1) could inhibit PRV by direct interaction with the virus particles in a dose-dependent manner and they could also protect the cells from PRV-induced apoptosis. Among the peptides tested, piscidin showed the strongest activity against PRV. Moreover, in vivo assay showed that piscidin can reduce the mortality of mice infected with PRV. CONCLUSION: In vitro and in vivo experiments indicate that piscidin has antiviral activity against PRV.


id: cord-321417-6code4oh
author: Benincasa, Monica
date: 2003-12-20
txt: ./txt/cord-321417-6code4oh.txt
cache: ./cache/cord-321417-6code4oh.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0196978103003462
doi: 10.1016/j.peptides.2003.07.025
summary:
  The parent peptides and mBMAP-28 analog protected mice from lethal i.p. infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index. Specifically, we analysed the in vitro activity of BMAP-27 and -28 and of their analogs against a wide panel of Gramnegative and -positive clinical isolates, also including many antibiotic-resistant strains, and against the human herpes simplex virus type 1 (HSV-1). The in vitro antibacterial activity of purified BMAP peptides and of their analogs was determined as the minimum inhibitory concentration (MIC) by a microdilution susceptibility test in 96-well microtiter plates, according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). The potential of BMAPs to protect mice from a bacterial challenge was tested in a model of acute peritonitis induced by i.p. injection of a lethal dose of P.

title:
  In vitro and in vivo antimicrobial activity of two α-helical cathelicidin peptides and of their synthetic analogs

abstract:
  Two α-helical antimicrobial peptides (BMAP-27 and -28) and four synthetic analogs were compared for in vitro and in vivo antimicrobial efficacy. All peptides proved active in vitro at micromolar concentrations against a range of clinical isolates, including antibiotic-resistant strains. BMAP-27 and two analogs were more effective towards Gram-negative, and BMAP-28 towards Gram-positive organisms. In addition, BMAP-28 provided some protection in vitro against human herpes simplex virus type 1 (HSV-1). The parent peptides and mBMAP-28 analog protected mice from lethal i.p. infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index.


id: cord-331633-ix5un6c9
title: Nanomedicines for the Delivery of Antimicrobial Peptides (AMPs)
author: Teixeira, Maria C.
date: 2020-03-20
url: https://www.ncbi.nlm.nih.gov/pubmed/32244858/
doi: 10.3390/nano10030560
abstract:
  Microbial infections are still among the major public health concerns since several yeasts and fungi, and other pathogenic microorganisms, are responsible for continuous growth of infections and drug resistance against bacteria. Antimicrobial resistance rate is fostering the need to develop new strategies against drug-resistant superbugs. Antimicrobial peptides (AMPs) are small peptide-based molecules of 5–100 amino acids in length, with potent and broad-spectrum antimicrobial properties. They are part of the innate immune system, which can represent a minimal risk of resistance development. These characteristics contribute to the description of these molecules as promising new molecules in the development of new antimicrobial drugs. However, efforts in developing new medicines have not resulted in any decrease of drug resistance yet. Thus, a technological approach on improving existing drugs is gaining special interest. Nanomedicine provides easy access to innovative carriers, which ultimately enable the design and development of targeted delivery systems of the most efficient drugs with increased efficacy and reduced toxicity. Based on performance, successful experiments, and considerable market prospects, nanotechnology will undoubtedly lead a breakthrough in biomedical field also for infectious diseases, as there are several nanotechnological approaches that exhibit important roles in restoring antibiotic activity against resistant bacteria.


id: cord-332003-67e9fchy
title: Delivery of therapeutic oligonucleotides with cell penetrating peptides()
author: Boisguérin, Prisca
date: 2015-06-29
txt: ./txt/cord-332003-67e9fchy.txt
cache: ./cache/cord-332003-67e9fchy.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0169409X15000198
doi: 10.1016/j.addr.2015.02.008
summary:
  Although challenged later on as detailed in Section 7, this mechanism and the possibility to use such so called cell-penetrating peptides (CPPs) as non-viral delivery vectors for biomolecules, fostered a very large interest. Since the chemical conjugation and purification of negatively charged ONs with the most popular cationic CPPs has turned out to be difficult, most applications have concerned chargeneutral ON analogues such as Peptide Nucleic Acids (PNAs) and PMO (see Section 3). Unexpectedly, in a well-characterized HeLa 705 cell assay with a positive read-out ( Fig. 1) , splicing redirection using PNA or PMO oligomers conjugated to various standard CPPs (Tat, Penetratin or oligo-arginines) was not achieved in our research groups [57] . This led to the development of several arginine-rich peptides as PMO conjugates for use in muscle cells and in vivo mouse models of DMD as outlined in Section 4.

abstract:
  Oligonucleotide-based drugs have received considerable attention for their capacity to modulate gene expression very specifically and as a consequence they have found applications in the treatment of many human acquired or genetic diseases. Clinical translation has been often hampered by poor biodistribution, however. Cell-penetrating peptides (CPPs) appear as a possibility to increase the cellular delivery of non-permeant biomolecules such as nucleic acids. This review focuses on CPP-delivery of several classes of oligonucleotides (ONs), namely antisense oligonucleotides, splice switching oligonucleotides (SSOs) and siRNAs. Two main strategies have been used to transport ONs with CPPs: covalent conjugation (which is more appropriate for charge-neutral ON analogues) and non-covalent complexation (which has been used for siRNA delivery essentially). Chemical synthesis, mechanisms of cellular internalization and various applications will be reviewed. A comprehensive coverage of the enormous amount of published data was not possible. Instead, emphasis has been put on strategies that have proven to be effective in animal models of important human diseases and on examples taken from the authors' own expertise.


id: cord-333262-xvfl7ycj
author: Robson, B.
date: 2020-04-11
txt: ./txt/cord-333262-xvfl7ycj.txt
cache: ./cache/cord-333262-xvfl7ycj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.compbiomed.2020.103749
doi: 10.1016/j.compbiomed.2020.103749
summary:
  The Wuhan and related isolates revealed a coronavirus that resides in the subgenus Sarbecovirus of the genus Betacoronavirus [2] , and although genetically distinct from its predecessor SARS-CoV it appeared to have similar external binding proteins, meaning here the spike glycoprotein discussed extensively in the present paper. In brief summary, the justifications for the ensemble pharmacophore in the coronavirus case, i.e. the contributions to "fuzziness", include parsimony, that proteins and parts of proteins sometimes have more than one function [12] encouraged by limited numbers of accessible sites (due to e.g. glycosylation) and exemplified by parallel alternative mechanisms of cell entry, multiple methods of drug action, escape from scientific defense measures by virus mutation, polymorphism of human proteins involved, different expression levels of human proteins involved, and the potential problem of the "specter of vaccine development" (concerns about missing the appropriate region of the virus that allows common cold viruses to escape the appropriate immune response).

title:
  COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance

abstract:
  Abstract This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2′ spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles’ Heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding studies. The enzyme 11β-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.


id: cord-337812-arivkkj0
author: Chu, Ling-Hon Matthew
date: 2006-03-07
url: https://www.ncbi.nlm.nih.gov/pubmed/16600962/
doi: 10.1110/ps.052007306
title:
  Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

abstract:
  Severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CL(pro)) mediates extensive proteolytic processing of replicase polyproteins, and is considered a promising target for anti-SARS drug development. Here we present a rapid and high-throughput screening method to study the substrate specificity of SARS-CoV 3CL(pro). Six target amino acid positions flanking the SARS-CoV 3CL(pro) cleavage site were investigated. Each batch of mixed peptide substrates with defined amino acid substitutions at the target amino acid position was synthesized via the “cartridge replacement” approach and was subjected to enzymatic cleavage by recombinant SARS-CoV 3CL(pro). Susceptibility of each peptide substrate to SARS-CoV 3CL(pro) cleavage was monitored simultaneously by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The hydrophobic pocket in the P2 position at the protease cleavage site is crucial to SARS-CoV 3CL(pro)-specific binding, which is limited to substitution by hydrophobic residue. The binding interface of SARS-CoV 3CL(pro) that is facing the P1′ position is suggested to be occupied by acidic amino acids, thus the P1′ position is intolerant to acidic residue substitution, owing to electrostatic repulsion. Steric hindrance caused by some bulky or β-branching amino acids in P3 and P2′ positions may also hinder the binding of SARS-CoV 3CL(pro). This study generates a comprehensive overview of SARS-CoV 3CL(pro) substrate specificity, which serves as the design basis of synthetic peptide-based SARS-CoV 3CL(pro) inhibitors. Our experimental approach is believed to be widely applicable for investigating the substrate specificity of other proteases in a rapid and high-throughput manner that is compatible for future automated analysis.


id: cord-337897-hkvll3xh
title: Peptide Bioinformatics- Peptide Classification Using Peptide Machines
author: Yang, Zheng Rong
date: 2009
url: https://www.ncbi.nlm.nih.gov/pubmed/19065810/
doi: 10.1007/978-1-60327-101-1_9
abstract:
  Peptides scanned from whole protein sequences are the core information for many peptide bioinformatics research subjects, such as functional site prediction, protein structure identification, and protein function recognition. In these applications, we normally need to assign a peptide to one of the given categories using a computer model. They are therefore referred to as peptide classification applications. Among various machine learning approaches, including neural networks, peptide machines have demonstrated excellent performance compared with various conventional machine learning approaches in many applications. This chapter discusses the basic concepts of peptide classification, commonly used feature extraction methods, three peptide machines, and some important issues in peptide classification.


id: cord-339879-92esdjy9
title: Phages and HIV-1: From Display to Interplay
author: Delhalle, Sylvie
date: 2012-04-13
txt: ./txt/cord-339879-92esdjy9.txt
cache: ./cache/cord-339879-92esdjy9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22606007/
doi: 10.3390/ijms13044727
summary:
  The BNtAb IgG1 b12 was the first neutralizing MAb selected from a phage-displayed Fab (antibody fragment composed of one constant and one variable domain of the heavy (CH1 and VH) and the light (CL and VL) chains linked together) library derived from an HIV-1-infected donor (See section 3.1.1.1.1.) [41] . At the end of the second round, selected phages displaying longer inserts of 40 to 50 AA corresponding to the N-and C-terminal regions of Gag were identified, revealing the presence of two distinct antigenic regions in Gag. This study demonstrated that gene-fragment phage display could be used to identify epitopes targeted by polyclonal Abs. Although they occur at a very low frequency in humans, antibodies targeting host proteins involved in HIV-1 infection have been reported in immunized animals. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries

abstract:
  The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.


id: cord-340970-389t032s
author: Choy, Wai-Yan
date: 2004-06-01
url: https://www.ncbi.nlm.nih.gov/pubmed/15044316/
doi: 10.1373/clinchem.2003.029801
title:
  Synthetic Peptide Studies on the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Glycoprotein: Perspective for SARS Vaccine Development

abstract:
  Background: The S (spike) protein of the etiologic coronavirus (CoV) agent of severe acute respiratory syndrome (SARS) plays a central role in mediating viral infection via receptor binding and membrane fusion between the virion and the host cell. We focused on using synthetic peptides for developing antibodies against SARS-CoV, which aimed to block viral invasion by eliciting an immune response specific to the native SARS-CoV S protein. Methods: Six peptide sequences corresponding to the surface regions of SARS-CoV S protein were designed and investigated by use of combined bioinformatics and structural analysis. These synthetic peptides were used to immunize both rabbits and monkeys. Antisera collected 1 week after the second immunization were analyzed by ELISA and tested for antibody specificity against SARS-CoV by immunofluorescent confocal microscopy. Results: Four of our six synthetic peptides (S2, S3, S5, and S6) elicited SARS-CoV-specific antibodies, of which S5 (residues 788–820) and S6 (residues 1002–1030) exhibited immunogenic responses similar to those found in a parallel investigation using truncated recombinant protein analogs of the SARS-CoV S protein. This suggested that our S5 and S6 peptides may represent two minimum biologically active sequences of the immunogenic regions of the SARS-CoV S protein. Conclusions: Synthetic peptides can elicit specific antibodies to SARS-CoV. The study provides insights for the future development of SARS vaccine via the synthetic-peptide-based approach.


id: cord-343791-0vykwml5
title: Progress towards the clinical translation of bio-inspired peptide and protein assemblies
author: Hainline, Kelly M.
date: 2017-11-08
txt: ./txt/cord-343791-0vykwml5.txt
cache: ./cache/cord-343791-0vykwml5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29115746/
doi: 10.1002/adhm.201700930
summary:
  These include spherical assemblies such as virus-like particles, designed protein nanoparticles, and peptide amphiphiles (Figure 1) ; and elongated structures such as β-sheet nanofibers, fiber-forming peptide amphiphiles, and filamentous phage (Figure 2) . [17, 18] Owing to their lack of a viral genome, VLP-based vaccines circumvent some risks associated Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. [19] As alternatives to these previous platforms, VLPs were developed to display an array of epitopes that mimic the surface of native viruses more effectively than subunit or peptide vaccines, thus improving their immunogenic properties. Whereas synthetic peptides are usually not sufficiently immunogenic and require adjuvants, the Burkhard group has developed a self-assembling protein nanoparticle platform that displays both B and T cell epitopes to produce a vaccine with self-adjuvanting qualities.

abstract:
  Supramolecular materials composed of proteins and peptides have been receiving considerable attention towards a range of diseases and conditions from vaccines to drug delivery. Owing to the relative newness of this class of materials, the bulk of work to date has been preclinical. However, examples of approved treatments particularly in vaccines, dentistry, and hemostasis are demonstrating the translational potential of supramolecular polypeptides. Here we describe critical milestones in the clinical development of this class of materials and describe currently approved supramolecular polypeptide therapies. Additional examples of not-yet-approved materials that are steadily advancing towards clinical use are also featured. Spherical assemblies such as virus-like particles (VLPs), designed protein nanoparticles, and spherical peptide amphiphiles are highlighted, followed by fiber-forming systems such as fibrillizing peptides, fiber-forming peptide-amphiphiles, and filamentous bacteriophages.


id: cord-346816-xys0g8b8
author: Shichijo, S.
date: 2004-10-20
url: https://www.ncbi.nlm.nih.gov/pubmed/15496204/
doi: 10.1111/j.1399-0039.2004.00314.x
title:
  Assessment of synthetic peptides of severe acute respiratory syndrome coronavirus recognized by long‐lasting immunity

abstract:
  Abstract: In order to determine highly immunogenic severe acute respiratory syndrome coronavirus (SARS‐CoV) epitope peptides capable of inducing long‐lasting immunity, we first screened immunoglobulin‐G (IgG) antibodies reactive to 197 different overlapping 15‐mers from the SARS‐CoV proteins in the sera of three infected patients. Forty‐two peptides among them were reactive to the sera from all three patients. Consequently, we tested for the reactivity of these 42 peptides to patients' sera (n = 45) at 6‐month post‐infection. The significantly higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42 peptides were detectable in the post‐infection sera from 23 (51%), 27 (60%) and 19 (42%) of 45 patients, respectively. These three peptides, recognized by their long‐lasting immunity, may provide a better understanding of the immunogenicity of SARS‐CoV.


id: cord-347661-q9lgliph
title: Production of Monospecific Rabbit Antisera Recognizing Nidovirus Proteins
author: Zevenhoven-Dobbe, Jessika C.
date: 2007-11-28
txt: ./txt/cord-347661-q9lgliph.txt
cache: ./cache/cord-347661-q9lgliph.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/19057875/
doi: 10.1007/978-1-59745-181-9_16
summary:
  The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. Furthermore, in the context of specific research questions, polyclonal antisera may sometimes even be preferred over monoclonal antibodies since they contain a mixture of immunoglobulin molecules, derived from different B-cell lines in the immunized animal, often recognizing multiple epitopes of the target protein. The antiserum used here was raised against a domain in the C-terminal region of pp1a of the arterivirus EAV (8) and recognizes a large set of processing intermediates and end products, which are indicated by arrowheads: (A) Western blot analysis: EAV-and mock-infected cell lysates were prepared at 8 h postinfection, run on an SDS-polyacrylamide gel, blotted to PVDF membrane, and incubated with the postimmune serum at a 1:1000 dilution.

abstract:
  The importance of monospecific antisera for the experimental analysis of viral proteins is undisputed. They make it possible to identify and analyze the target protein against a background of a large number of other proteins, either in whole fixed cells or in cell lysates. This chapter describes our experience with the production of such rabbit antisera directed against proteins of coronaviruses and other nidoviruses. The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. For screening of the immune response following immunization, detailed protocols for three commonly used techniques are described, all of which are based on the use of infected cells or cells expressing the protein of interest, side by side with appropriate controls. The in situ immunodetection of the target in fixed cells by immunofluorescence microscopy is described, as are protocols for techniques that can be applied to cell lysates containing the target protein (Western blotting and immunoprecipitation). The latter techniques are performed in combination with polyacrylamide gel electrophoresis, thus allowing confirmation of the molecular weight of the target that is recognized by the antiserum.


id: cord-348432-6jgao58w
title: Biomaterials Made from Coiled-Coil Peptides
author: Conticello, Vincent
date: 2017-01-19
url: https://doi.org/10.1007/978-3-319-49674-0_17
doi: 10.1007/978-3-319-49674-0_17
abstract:
  The development of biomaterials designed for specific applications is an important objective in personalized medicine. While the breadth and prominence of biomaterials have increased exponentially over the past decades, critical challenges remain to be addressed, particularly in the development of biomaterials that exhibit highly specific functions. These functional properties are often encoded within the molecular structure of the component molecules. Proteins, as a consequence of their structural specificity, represent useful substrates for the construction of functional biomaterials through rational design. This chapter provides an in-depth survey of biomaterials constructed from coiled-coils, one of the best-understood protein structural motifs. We discuss the utility of this structurally diverse and functionally tunable class of proteins for the creation of novel biomaterials. This discussion illustrates the progress that has been made in the development of coiled-coil biomaterials by showcasing studies that bridge the gap between the academic science and potential technological impact.


id: cord-351321-6d2mn5ok
author: Gouveia, Duarte
date: 2020-06-19
url: https://doi.org/10.1101/2020.06.19.161000
doi: 10.1101/2020.06.19.161000
title:
  Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window

abstract:
  Rapid but yet sensitive, specific and high-throughput detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples is key to diagnose infected people and to better control the spread of the virus. Alternative methodologies to PCR and immunodiagnostic that would not require specific reagents are worth to investigate not only for fighting the COVID-19 pandemic, but also to detect other emergent pathogenic threats. Here, we propose the use of tandem mass spectrometry to detect SARS-CoV-2 marker peptides in nasopharyngeal swabs. We documented that the signal from the microbiota present in such samples is low and can be overlooked when interpreting shotgun proteomic data acquired on a restricted window of the peptidome landscape. Simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC-MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. We argue that peptides ADETQALPQR and GFYAQGSR from the nucleocapsid protein are of utmost interest as their signal is intense and their elution can be obtained within a 3 min window in the tested conditions. These results pave the way for the development of time-efficient viral diagnostic tests based on mass spectrometry.


id: cord-353815-w35spqqt
author: Huan, Yuchen
date: 2020-10-16
txt: ./txt/cord-353815-w35spqqt.txt
cache: ./cache/cord-353815-w35spqqt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33178164/
doi: 10.3389/fmicb.2020.582779
summary:
  This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. Tryptophan (Trp), as a non-polar amino acid, has a remarkable effect on the interface region of the lipid bilayer, whereas Arg, as a basic amino acid, confers peptide charge and hydrogen bond interactions, which are essential properties to combine with the bacterial membrane''s abundant anionic component. And it seems that Trp residues play the role of natural aromatic activators of Arg-rich AMPs by ion-pair-π interactions (Walrant et al., 2020) , thereby promoting enhanced peptide-membrane interactions (Chan et al., 2006) . Furthermore, L4H4, which is designed based on the linear cationic amphiphilic peptide magainin, also shows good antibacterial activity and cell penetration properties by inserting four histidine sequences in leucine and alanine (Lointier et al., 2020) .

title:
  Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

abstract:
  Antimicrobial peptides (AMPs) are a class of small peptides that widely exist in nature and they are an important part of the innate immune system of different organisms. AMPs have a wide range of inhibitory effects against bacteria, fungi, parasites and viruses. The emergence of antibiotic-resistant microorganisms and the increasing of concerns about the use of antibiotics resulted in the development of AMPs, which have a good application prospect in medicine, food, animal husbandry, agriculture and aquaculture. This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. The research progress on antivirus peptides, especially anti-coronavirus (COVID-19) peptides, has been introduced given the COVID-19 pandemic worldwide in 2020.


