Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:360

Article

Jesus Sanchez-Martin, Maria¹  Hristova, Kalina²  Pujol, Montserrat¹  Gomara, Maria J.³  Haro, Isabel³  Asuncion Alsina, M.¹  Antonia Busquets, M.¹ 

[1] Univ Barcelona, Fac Pharm, Dept Phys Chem, Associated Unit CSIC Peptides & Prot Physicochem, E-08028 Barcelona, Spain

[2] Johns Hopkins Univ, Dept Mat Sci & Engn, Baltimore, MD 21218 USA

[3] CSIC, IQAC, Dept Biomed Chem, Unit Synth & Biomed Applicat Peptides, ES-08034 Barcelona, Spain

关键词: HIV-1 FP inhibition;    Hepatitis G virus;    Peptide synthesis;    Bilayers as model membranes;    Giant unilamellar vesicles;    Confocal microscopy;   

DOI  :  10.1016/j.jcis.2011.04.053

来源: Elsevier

【 摘 要 】

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 El of the hepatitis G virus (GBV-C). Five of the El synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCL VALGCTICTD (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 El 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 El 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 El 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. (C) 2011 Elsevier Inc. All rights reserved.

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