HIV-1 Inhibiting Capacity of Novel Forms of Presentation of GB Virus C Peptide Domains is Enhanced by Coordination to Gold Compounds

María   J.   Gómara; Ramona      Galatola; Alejandro      Gutiérrez; María   C.   Gimeno; José   M.   Gatell; Víctor      Sánchez-Merino; Eloísa      Yuste; Isabel      Haro

Abstract

Following the report of beneficial effects of co-infection by GB virus C (GBV-C) for HIV-infected patients, we have studied synthetic GBV-C peptides and their relationship with HIV type-1. This paper reports the design and synthesis of new forms of presentation of two peptide inhibitors corresponding to the envelope proteins E1 and E2 of GBV-C, together with a study of their anti-HIV-1 activity. Homogeneous and heterogeneous multiple antigenic peptides (MAPs), lipophilic derivatizations, cyclization and peptide–gold conjugations are the chemical design strategies adopted. Our aim is to enhance the anti-viral potency of the GBV-C peptide domains. Of all the GBV-C peptide derivatives studied, peptide–gold complexes derived from the (22-39) sequence of the GBV-C E1 protein were the most active entry inhibitors. These results support the putative modulation of HIV-1 infection by the GBV-C E1 protein and open new perspectives for the development of novel peptide-derived HIV-1 entry inhibitors.

Keywords: Anti-HIV assays, cell–cell fusion assays, cyclic peptides, GBV-C, HIV-1, lipopeptides, multiple antigenic peptides, peptide–gold complexes.