A cyclic GB virus C derived peptide with anti-HIV-1 activity targets the fusion peptide of HIV-1
Ramona Galatola, Aimee Vasconcelos, Yolanda Pérez, Antonio Cruz, Montserrat Pujol, María A. Alsina, María J. Gómara, Isabel Haro
European Journal of Medicinal Chemistry
The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22–39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain of the HIV-1 gp41 protein in target cell membranes.
Circular dichroism, Secondary structure, Ligand binding, Vesicle interactions, Biochemistry, Medicinal