STUDIES ON THE C-TERMINAL OF HEXAPEPTIDE INHIBITORS OF THE HEPATITIS-C VIRUS SERINE-PROTEASE

Replacememt of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS 4A 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 carboxyl ic acids are specific. Norvaline was identified as a chemically stable replacement for the P1 residue of Ac-DDIVPC-OH which was also compati ble with activated carbonyl functionalities. (C) 1998 Elsevier Science Ltd. All rights reserved.