Physicochemical characterization of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide: Interaction with model membranes
Maria Jesús Sánchez-Martín, Antonio Cruz, M. Antònia Busquets, Isabel Haro, M. Asunción Alsina, Montserrat Pujol
International Journal of Pharmaceutics
Four peptide sequences corresponding to the E1 protein of GBV-C: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10) and QAGLAVRPGKSAAQLVGE (P18) were studied as they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP). In this work, the surface properties of the E1 peptide sequences are investigated and their physicochemical characterization is done by studying their interaction with model membranes; moreover, their mixtures with HIV-1 FP were also studied in order to observe whether they are capable to modify the HIV-1 FP interaction with model membranes as liposomes or monolayers. Physicochemical properties of peptides (pIand net charge) were predicted showing similarities between P7 and P8, and P10 and HIV-1 FP, whereas P18 appears to be very different from the rest. Circular dichroism experiments were carried out showing an increase of the percentage of α-helix of P7 and P8 when mixed with HIV-1 FP corroborating a conformational change that could be the cause of their inhibition ability. Penetration experiments show that all the peptides can spontaneously insert into phospholipid membranes. Analysis of compression isotherms indicates that the peptides interact with phospholipids and the E1 peptides modify the compression isotherms of HIV-1 FP, but there is one of the peptides that excelled as the best candidate for inhibiting the activity of HIV-1 FP, P7, and therefore, that could be potentially used in future anti-HIV-1 research.
Circular dichroism, Secondary structure, Vesicle interactions, Ligand binding, Biochemistry