title: Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C.
abstract: The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein E1 of the hepatitis G virus (GBV-C). Five of the E1 synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these E1 peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between E1 peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides. Our results highlight that these E1 synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS.
authors.affiliation: Physical Chemistry Department, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. mjsanchez@ub.edu
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Sánchez-Martín
authors.forename: Kalina
authors.initials: K
authors.lastname: Hristova
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pujol
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gómara
authors.forename: Isabel
authors.initials: I
authors.lastname: Haro
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Alsina
authors.forename: M Antònia
authors.initials: MA
authors.lastname: Busquets
mesh_terms: D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D019590:Nucleocapsid Proteins / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D013499:Surface Properties
chemical_list: D015700:HIV Envelope Protein gp41; D019590:Nucleocapsid Proteins; D009842:Oligopeptides; C099600:nucleocapsid protein, Hepatitis virus