title: A cyclic GB virus C derived peptide with anti-HIV-1 activity targets the fusion peptide of HIV-1.
abstract: 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.
authors.affiliation: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: Ramona
authors.initials: R
authors.lastname: Galatola
authors.affiliation: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: Aimee
authors.initials: A
authors.lastname: Vasconcelos
authors.affiliation: NMR Unit, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Pérez
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Biology, University Complutense of Madrid, 28040 Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Department of Physical Chemistry, Associated Unit to CSIC, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pujol
authors.affiliation: Department of Physical Chemistry, Associated Unit to CSIC, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Alsina
authors.affiliation: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Gómara
authors.affiliation: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain. Electronic address: isabel.haro@iqac.csic.es.
authors.forename: Isabel
authors.initials: I
authors.lastname: Haro
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D029407:GB virus C / Q000737:chemistry*; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments
keywords: Biophysical assays; E1 peptide; Fusion peptide; GB virus C; Human immunodeficiency virus type 1; Peptides interaction