The effect of fusion inhibitors on the phase behaviour of N-methylated dioleoylphosphatidylethanolamine

The effects of two fusion inhibitors on the lipid polymorphism of N-methylated dioleoylphosphatidylethanolamine were studied using temperature-resolved, small-angle X-ray diffraction. The inhibitory role of the tri-peptide carbobenzoxy-D-phenylalanine-L-phenylalanine-glycine and the lipid 1-lauroyl-2-hydroxy-sn-glycero-3-phosphocholine in the fusion pathway was studied, using the non-lamellar phase behaviour of the lipid as a model. We used p15EK, the N-terminal region of gp41 from feline leukaemia virus as promoter of membrane fusion, and measured the structural parameters of each observed lipid phase as a function of temperature. The fusion inhibitors were found to impede the expression of negative curvature of lipid monolayers even in the presence of fusion peptide. The results of this study are interpreted in relation to models of the membrane fusion mechanism.