Interaction of a peptide deriving from the glycoprotein gp36 of the feline immunodeficiency virus and its lipoylated analogue with phospholipid membranes: an ESR study

P59, a 20-mer peptide modelled on the membrane-proximal external region (MPER) of the FIV gp36 ectodomain, has potent antiviral activity. The lipoylated analogue, lipo-P59, displays a similar activity, which is maintained for longer times under more severe external conditions. A mechanism has been recently proposed in which the peptide, being positioned on the surface of the cell membrane, inhibits its fusion with the virus; the lipophilic chain of lipo-P59 is supposed to insert into the membrane interior, thus anchoring the peptide at the surface, so that the antiviral activity persists for a longer time. In an attempt to gain deeper insight into the positioning of P59 and lipo-P59 with respect to lipidic membranes, a spin-label electron spin resonance (ESR) spectroscopy investigation was undertaken, the results of which are reported in the present poster. ESR spectroscopy of spin-labeled lipids is especially well suited for investigating lipid-protein and lipid-peptide interaction. The interactions of P59 and lipo-P59 with both zwitterionc and negatively charged lipid bilayer membranes, formed by dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylglycerol (DMPG), have been investigated by using phospholipid ESR probes that are labelled at different positions in the sn-2 acyl chain. It is found that P59 presents a de-structuring effect on the membranes, caused by the synergy of hydrophobic and electrostatic interactions between the peptide and the lipids. At high P59 concentration the mambranes break, forming smaller aggregates. In contrast, lipo-P59 inserts its hydrophobic chain into the bilayer core, while the aminoacidic chain remais extended onto the bylayer surface, exposed to the external medium, thus explaining its better antiviral activity.