Physicochemical characterization of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide: Interaction with model membranes

Abstract

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 (pI and 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.

Understanding Dengue Virus Capsid Protein Disordered N-Terminus and pep14-23-Based Inhibition

“…Tensiometry (Supporting Information Figure S2A) and zeta potential (Supporting Information Figure S2B) measurements showed that the peptide interacts both with monolayers and bilayers of POPG in the presence of K + ions similarly to what it does in the presence of Na + ions. Following previous approaches, ,, the data were fitted using the equations displayed in Table . Briefly, lipid monolayers were tested by tensiometry measurements and LUV were used both in zeta potential and in CD measurements.…”

“… a Following previous approaches, ,, the data were fitted using the equations displayed below. The half-maximal effect ( K D app ) represents an apparent binding constant (not directly comparable between techniques).…”

“…pep14-23 Shows an α-Helical NMR Structure. To further confirm the α-helical tendency of pep14-23, we used NMR spectroscopy to determine the structure of pep14-23 in the presence of dodecylphosphocholine (DPC) micelles (Figure 3; statistics details are available in Supporting a Following previous approaches, 18,27,28 the data were fitted using the equations displayed below. The half-maximal effect (K D app ) represents an apparent binding constant (not directly comparable between techniques).…”

A study of HIV-1 FP inhibition by GBV-C peptides using lipid nano-assemblies

“…Surface behaviour at the air-water interface [15][16][17], and in peptide-lipid binding assays [11,18,19], leakage assays, fluorescence anisotropy or fluorescence resonance energy transfer studies [20,21] have each been applied to find a correlate between the capacity to inhibit HIV-1 FP in vitro and in vivo during cell-cell fusion inhibition studies [10,15]. In addition, topographical characterisation of model membranes showing the changes caused by HIV-1 FP or GBV-C peptides in various mixtures have been obtained by fluorescence microscopy (FM) and atomic force microscopy (AFM) [22,23]. However, the inhibitory effect of GBV-C peptides on HIV-1 FP has not been clearly elucidated yet.…”

“…It could be that it is due to the interaction of both peptides prior to interaction with the membrane, or because the GBV-C peptides interact with the membrane, preventing binding of the fusion peptide and entry to the host cell. The inhibitory effect on HIV-1 FP of GBV-C sequence SDRDTVVELSEWGVPCAT (P45), which belongs to the E2 structural protein, has been studied in both cell-cell inhibition and in vitro lipid-peptide interaction assays, showing good agreement when supported lipid bilayers (SLBs) and AFM were used [12,22,23].…”