Novel Peptide Mimetics Based on N-protected Amino Acids Derived from Isomannide as Potential Inhibitors of NS3 Serine Protease of Hepatitis C Virus

Title:Novel Peptide Mimetics Based on N-protected Amino Acids Derived from Isomannide as Potential Inhibitors of NS3 Serine Protease of Hepatitis C Virus

Volume: 9 Issue: 4

Author(s): Thalita G. Barros, Bruna C. Zorzanelli, Sergio Pinheiro, Monique A. de Brito, Amilcar Tanuri, Emmerson C.B. da Costa, Ronaldo S. Mohana-Borges, Carlos R. Rodrigues, Alessandra T.M. Souza and Vitor F. Ferreira, Estela M.F. Muri

Affiliation:

Keywords: HCV, isomannide, peptide mimetic, serine protease, hepatocellular carcinoma, structural manipulation, bioavailability, administration, dipeptides, scaffold

Abstract: Hepatitis C virus (HCV) is among the most important flaviviruses. It has a serine protease which is important for viral replication and this enzyme constitutes a suitable target for new anti-retroviral drugs. Herein we disclose a series of amide and ester peptide mimetic inhibitors of serine proteases, all of them obtained via coupling reactions of isomannide derivatives with N-protected amino acids. The arginine derivative 19 showed 45% of inhibition of NS3/4A serine protease at 100 μM and molecular modeling studies had shown that 19 interacted with the active site of this enzyme.

Cite this article as:

Thalita G. Barros, Bruna C. Zorzanelli, Sergio Pinheiro, Monique A. de Brito, Amilcar Tanuri , Emmerson C.B. da Costa, Ronaldo S. Mohana-Borges, Carlos R. Rodrigues, Alessandra T.M. Souza and Vitor F. Ferreira, Estela M.F. Muri , Novel Peptide Mimetics Based on N-protected Amino Acids Derived from Isomannide as Potential Inhibitors of NS3 Serine Protease of Hepatitis C Virus, Letters in Organic Chemistry 2012; 9 (4) . https://dx.doi.org/10.2174/157017812800233787