The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease

J Med Chem. 2004 Dec 16;47(26):6443-6. doi: 10.1021/jm049435d.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Crystallography, X-Ray
  • Hepacivirus / enzymology*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Structure
  • Oligopeptides / chemistry*
  • Protein Binding
  • Stereoisomerism
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / chemistry*

Substances

  • Antiviral Agents
  • Indoles
  • NS3 protein, hepatitis C virus
  • Oligopeptides
  • Viral Nonstructural Proteins