Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease

Bioorg Med Chem Lett. 1998 Oct 6;8(19):2719-24. doi: 10.1016/s0960-894x(98)00480-6.


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.

MeSH terms

  • Cysteine / chemistry
  • Cysteine / pharmacology
  • Hepacivirus / enzymology*
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*


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