1.
J Med Chem
; 48(16): 5088-91, 2005 Aug 11.
Artigo
em Inglês
| MEDLINE
| ID: mdl-16078825
RESUMO
Hepatitis C virus (HCV) NS3, when bound to NS-4A cofactor, facilitates development of mature virons by catalyzing cleavage of a polyprotein to form functional and structural proteins of HCV. The enzyme has a shallow binding pocket at the catalytic site, making development of inhibitors difficult. We have designed, preorganized, and depeptidized macrocyclic inhibitors from P(4) to P(2)' and optimized binding to 0.1 microM. The structure of an inhibitor bound to the enzyme was also solved.