title: Potent inhibitors of the hepatitis C virus NS3 protease: design and synthesis of macrocyclic substrate-based beta-strand mimics.
abstract: The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring beta-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.
authors.affiliation: Department of Chemistry, Boehringer Ingelheim Ltd., Research and Development, 2100 Cunard Street, Laval, Quebec, Canada H7S 2G5.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goudreau
authors.forename: Christian
authors.initials: C
authors.lastname: Brochu
authors.forename: Dale R
authors.initials: DR
authors.lastname: Cameron
authors.forename: Jean-Simon
authors.initials: JS
authors.lastname: Duceppe
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Faucher
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ferland
authors.forename: Chantal
authors.initials: C
authors.lastname: Grand-Maître
authors.forename: Martin
authors.initials: M
authors.lastname: Poirier
authors.forename: Bruno
authors.initials: B
authors.lastname: Simoneau
authors.forename: Youla S
authors.initials: YS
authors.lastname: Tsantrizos
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D018716:Molecular Mimicry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D011480:Protease 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