TY - JOUR
T1 - Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C
AU - Sánchez-Martín, Maria Jesús
AU - Hristova, Kalina
AU - Pujol, Montserrat
AU - Gómara, Maria J.
AU - Haro, Isabel
AU - Asunción Alsina, M.
AU - Antònia Busquets, M.
N1 - Funding Information:
This study was supported by project CTQ2006-15396-C02-02/01-BQU from the Secretaría de Estado de Investigación, Ministerio de Ciencia e Innovación, Dirección General de Programas y transferencia de conocimiento, Subdirección General de Proyectos de Investigación (Spain), and supported in part by NIH grant GM 068619. M.J. Sánchez-Martín is a recipient of an FPI program pre-doctoral grant. The authors are members of the consolidated research group by the Generalitat de Catalunya: Peptides and Proteins: physicochemical studies (2005SGR00278). The authors thank Dr. Marta Taulés Marín, of the Confocal Microscopy and Cellular Micromanipulation Unit, and Dr. Rafel Prohens López of the Fine Chemistry Unit, from the Barcelona Science Park, for heir invaluable assistance.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
KW - Bilayers as model membranes
KW - Confocal microscopy
KW - Giant unilamellar vesicles
KW - HIV-1 FP inhibition
KW - Hepatitis G virus
KW - Peptide synthesis
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U2 - 10.1016/j.jcis.2011.04.053
DO - 10.1016/j.jcis.2011.04.053
M3 - Article
C2 - 21565353
AN - SCOPUS:79957849110
SN - 0021-9797
VL - 360
SP - 124
EP - 131
JO - Journal of Colloid And Interface Science
JF - Journal of Colloid And Interface Science
IS - 1
ER -