A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease

Bioorg Med Chem Lett. 2002 Feb 25;12(4):701-4. doi: 10.1016/s0960-894x(01)00842-3.

Abstract

The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibitors (6, K(i) 0.5 nM; and 8 K*(i) 10 pM).

MeSH terms

  • Cysteine*
  • Drug Design
  • Hepacivirus / enzymology*
  • Humans
  • Models, Molecular*
  • Molecular Mimicry
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • NS3 protein, hepatitis C virus
  • Oligopeptides
  • Viral Nonstructural Proteins
  • Cysteine