Abstract
Truncation and substitution SAR studies of azapeptide-based inhibitors of the Hepatitis C virus (HCV) NS3 serine protease have been performed. These azapeptides were designed from the HCV polyprotein's NS5A-NS5B trans cleavage junction and contained an azaamino acid residue at the P1 position. These azapeptides exhibited predominantly non-acylating, competitive inhibition, contrary to classical azapeptides.
MeSH terms
-
Aza Compounds / pharmacology*
-
Binding Sites
-
Binding, Competitive
-
Hepacivirus / enzymology*
-
Models, Molecular
-
Serine Endopeptidases / drug effects*
-
Serine Endopeptidases / metabolism
-
Serine Proteinase Inhibitors / pharmacology*
-
Structure-Activity Relationship
-
Substrate Specificity / genetics
-
Viral Nonstructural Proteins / antagonists & inhibitors*
-
Viral Nonstructural Proteins / metabolism
Substances
-
Aza Compounds
-
NS3 protein, hepatitis C virus
-
Serine Proteinase Inhibitors
-
Viral Nonstructural Proteins
-
Serine Endopeptidases