id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-010203-dt9m596i	Hellen, Christopher U.T.	Viral proteases as targets for chemotherapeutic intervention	2004-08-26		.txt	text/plain	3196	154	37	Many human and animal viruses encode proteinases that play important roles at different stages in the infection cycle, including separation of functionally different domains from a precursor polyprotein (enabling cleavage products to be transported to different cellular compartments) and regulation of a variety of events in viral replication, such as uncoating, activation of replicative enzymes and morphogenesis [1] . Statine-based (I), reduced amide (II) and phosphinate (III) transition state analogues exhibited modest potency, but placement of Phe-Gly hydroxyethylene dipeptide isosteres (IV) into the consensus template yielded compounds that inhibited HIV PR at nanomolar concentrations in vitro and prevented polyprotein processing, virion maturation and viral spread at 25-100btM in cell culture. Truncation and extensive structure-activity analysis at the P1, PI" and P2' positions led to the identification of highly potent (subnanomolar) PR inhibitors based on dihydroxyethylene (V) [12-] and hydroxyethylene (IV) [13"] isostere transition state analogues.	./cache/cord-010203-dt9m596i.txt	./txt/cord-010203-dt9m596i.txt