title: The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease.
abstract: The design of a series of peptidomimetic inhibitors of the hepatitis C virus NS3 protease is described. These inhibitors feature an indoline-2-carboxamide as a novel heterocyclic replacement for the P3 amino acid residue and N-terminal capping group of tripeptide based inhibitors. The crystal structure of the ternary NS3/NS4A/inhibitor complex for the most active molecule in this series highlights its suitability as an N-terminal capping group of a dipeptide inhibitor of the NS3 protease.
authors.affiliation: IRBM-MRL Rome, Via Pontina km 30,600, 00040 Rome, Italy.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Ontoria
authors.forename: Stefania
authors.initials: S
authors.lastname: Di Marco
authors.forename: Immacolata
authors.initials: I
authors.lastname: Conte
authors.forename: M Emilia
authors.initials: ME
authors.lastname: Di Francesco
authors.forename: Cristina
authors.initials: C
authors.lastname: Gardelli
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Victor G
authors.initials: VG
authors.lastname: Matassa
authors.forename: Marco
authors.initials: M
authors.lastname: Poma
authors.forename: Christian
authors.initials: C
authors.lastname: Steinkühler
authors.forename: Cinzia
authors.initials: C
authors.lastname: Volpari
authors.forename: Steven
authors.initials: S
authors.lastname: Harper
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000201:enzymology*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D011485:Protein Binding; D013237:Stereoisomerism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D009842:Oligopeptides; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases