1. Biophysical investigations of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide.
- Author
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Sánchez-Martín MJ, Urbán P, Pujol M, Haro I, Alsina MA, and Busquets MA
- Subjects
- 3T3 Cells, Amino Acid Sequence, Animals, Biophysics, Cell Survival drug effects, Circular Dichroism, Erythrocytes drug effects, GB virus C metabolism, HIV Envelope Protein gp41 chemistry, HIV Fusion Inhibitors chemical synthesis, HIV Fusion Inhibitors chemistry, HIV Fusion Inhibitors toxicity, Hemolysis drug effects, Humans, Membrane Fusion drug effects, Mice, Microscopy, Atomic Force, Microscopy, Electron, Scanning, Molecular Sequence Data, Peptides chemical synthesis, Peptides chemistry, Peptides toxicity, Protein Conformation, Surface Plasmon Resonance, Surface Properties, Unilamellar Liposomes chemistry, GB virus C chemistry, HIV Envelope Protein gp41 antagonists & inhibitors, HIV Fusion Inhibitors pharmacology, HIV-1, Peptides pharmacology
- Abstract
Five peptide sequences corresponding to the E1 protein of GBV-C [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle interaction. In this work the interaction of these peptides with the HIV-1 FP, as well as with membrane models, was analyzed to corroborate their inhibition ability and to understand if the interaction with the fusion peptide takes place in solution or at the membrane level. Several studies were carried out on aggregation and membrane fusion, surface Plasmon resonance, and conformational analysis by circular dichroism. Moreover, in vitro toxicity assays, including cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood cells, were performed to evaluate if these peptides could be potentially used in anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we decided to discard it for futures studies. P18 and P22 do not inhibit membrane fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus we have not discarded them yet. P7 and P8 were selected as the best candidates for future studies because they are capable of inhibiting membrane fusion and the interaction of HIV-1 FP with bilayers. Therefore, these peptides could be potentially used in future anti-HIV-1 research., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2011
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