Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.
Replacement of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS4A peptide cofactor) by activated carbonyl groups does not produce any substantial increase in potency. These latter inhibitors also inhibit a variety of other serine and cysteine proteases whereas the carboxylic acids are specific. Norvaline was identified as a chemically stable replacement for the P1 residue of Ac-DDIVPC-OH which was also compatible with activated carbonyl functionalities.
Llinàs-Brunet
M
M
Boehringer Ingelheim (Canada) Ltd, Bio-Méga Research Division, Laval, Québec, Canada.
Bailey
M
M
Déziel
R
R
Fazal
G
G
Gorys
V
V
Goulet
S
S
Halmos
T
T
Maurice
R
R
Poirier
M
M
Poupart
M A
MA
Rancourt
J
J
Thibeault
D
D
Wernic
D
D
Lamarre
D
D
D003545:Cysteine / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000201:enzymology*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; 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
D003545:Cysteine; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases