id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-318738-7dgbc4um	Schmidt, Marco Florian	Sensitized Detection of Inhibitory Fragments and Iterative Development of Non‐Peptidic Protease Inhibitors by Dynamic Ligation Screening	2008-03-17		.txt	text/plain	1957	93	47	A potential anti‐SARS drug has been developed by dynamic ligation screening (DLS), by which nucleophilic fragments are directed to the protein's active site by reversible reaction with an aldehyde inhibitor. To establish DLS for site-directed identification of inhibitory fragments, at first a fluorescence-based assay [4] for SARS-CoV M pro activity was developed by employing the substrate Ac-TSAVLQ-AMCA (1). To obtain an entirely non-peptidic inhibitor of SARS-CoV M pro targeting both the S1' and S1 pockets, the dynamic ligation screening was conducted iteratively in a "reverted" mode ( Table 2 ). Dynamic ligation screening for the S1' site was performed for a library of 234 nucleophilic fragments using 1 mm of SARS-CoV M pro , 200 mm 1, 400 mm of one nucleophilic fragment per well, and 50 mm of the peptide aldehyde inhibitor Ac-DSFDQ-H (2) on a 384-well microtiter plate.	./cache/cord-318738-7dgbc4um.txt	./txt/cord-318738-7dgbc4um.txt