id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-006087-hynkb0a8	Acharya, K. Ravi	Ace revisited: A new target for structure-based drug design	2003		.txt	text/plain	8130	386	47	Current-generation angiotensin-converting enzyme (ACE) inhibitors are widely used for cardiovascular diseases, including high blood pressure, heart failure, heart attack and kidney failure, and have combined annual sales in excess of US $6 billion. Some differences in catalytic properties have been observed for these two sites: the N-domain site is notably 50-times more active toward the haemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) 21 , 1000-times Here, we provide an overview of ACE and the RAS, current ACE inhibitors and their clinical utility, insights from the tACE crystal structure, and the rationale and prospects for developing second-generation, domainselective inhibitors by structure-guided design. BPF was a mixture of peptides 59 , which were shown to be potent and specific inhibitors of ACE (TABLE 1), and structure-activity studies indicated that the optimal C-terminal inhibitory sequence was Phe-Ala-Pro 60 . An important caveat in considering the design and pharmacological utility of domain-selective ACE inhibitors is the potential for conformational effects that have not yet been observed in the tACE crystal structure.	./cache/cord-006087-hynkb0a8.txt	./txt/cord-006087-hynkb0a8.txt