The Role of an Amphiphilic Capping Group in Covalent and Non-Covalent Dipeptide Inhibitors of HCV NS3 Serine Protease

The analysis of the S3 binding region of the Hepatitis C Virus NS3 serine protease allowed replacing the P3 amino acid of alpha-ketoacid tripeptide inhibitors with an amphiphilic capping group. The binding mode of alpha-ketoacid (8) (IC50 = 1 mu M) and the role of the amphiphilic group in non-covalent phenethylamide inhibitor (15) (IC50 = 21 mu M) will be discussed.