Structural requirements for the inhibition of membrane fusion by carbobenzoxy- d-Phe-Phe-Gly

Abstract

The peptide ZfFG is known to inhibit non-bilayer phase formation as well as vesicle-vesicle and viral fusion. In order to ascertain some of the properties or structural features of this peptide which were important for the inhibition of membrane fusion, the blocking group was transferred from the amino to the carboxyl end to make fFGOBz. The fFGOBz lowered the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine and it promoted the formation of isotropic phases in monomethyldioleoylphosphatidylethanolamine. The promotion of non-bilayer phases by fFGOBz appeared to be enhanced by a charged terminal amino group as higher pH or formylation of the amino group both decreased the effectiveness of this peptide to induce formation of the hexagonal phase. With the monomethyldioleoylphosphatidylethanolamine, the fFGOBz also promoted vesicle leakage and fusion as measured by lipid intermixing. The fFGOBz did not inhibit the formation of lipid structures of high curvature, resulting from sonication of phosphatidylcholine, as did ZfFG. Thus, the effects of fFGOBz on membranes are in sharp contrast to those of ZfFG and more closely resemble the behaviour of larger fusion peptides corresponding to the amino-terminal segment of viral fusion proteins. Our results demonstrate that having the carbobenzoxy group on the amino-terminus of fFG is important for giving the peptide derivative the property of inhibiting membrane fusion.