Solid-phase synthesis of peptidomimetic inhibitors for the hepatitis C virus NS3 protease.
The NS3 serine protease enzyme of the hepatitis C virus (HCV) is essential for viral replication. Short peptides mimicking the N-terminal substrate cleavage products of the NS3 protease are known to act as weak inhibitors of the enzyme and have been used as templates for the design of peptidomimetic inhibitors. Automated solid-phase synthesis of a small library of compounds based on such a peptidomimetic scaffold has led to the identification of potent and highly selective inhibitors of the NS3 protease enzyme.
Poupart
M A
MA
Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., Quebec H7S 2G5, Canada.
Cameron
D R
DR
Chabot
C
C
Ghiro
E
E
Goudreau
N
N
Goulet
S
S
Poirier
M
M
Tsantrizos
Y S
YS
D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D019151:Peptide Library; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019151:Peptide Library; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases