title: Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.
abstract: 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.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd, Bio-Méga Research Division, Laval, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Llinàs-Brunet
authors.forename: M
authors.initials: M
authors.lastname: Bailey
authors.forename: R
authors.initials: R
authors.lastname: Déziel
authors.forename: G
authors.initials: G
authors.lastname: Fazal
authors.forename: V
authors.initials: V
authors.lastname: Gorys
authors.forename: S
authors.initials: S
authors.lastname: Goulet
authors.forename: T
authors.initials: T
authors.lastname: Halmos
authors.forename: R
authors.initials: R
authors.lastname: Maurice
authors.forename: M
authors.initials: M
authors.lastname: Poirier
authors.forename: M A
authors.initials: MA
authors.lastname: Poupart
authors.forename: J
authors.initials: J
authors.lastname: Rancourt
authors.forename: D
authors.initials: D
authors.lastname: Thibeault
authors.forename: D
authors.initials: D
authors.lastname: Wernic
authors.forename: D
authors.initials: D
authors.lastname: Lamarre
mesh_terms: 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
chemical_list: 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