STRUCTURAL REQUIREMENTS FOR THE INHIBITION OF MEMBRANE-FUSION BY CARBOBENZOXY-D-PHE-PHE-GLY

The peptide ZfFG is known to inhibit non-bilayer phase formation as we ll as vesicle-vesicle and viral fusion. In order to ascertain some of the properties or structural features of this peptide which were impor tant for the inhibition of membrane fusion, the blocking group was tra nsferred from the amino to the carboxyl end to make fFGOBz. The fFGOBz lowered the bilayer to hexagonal phase transition temperature of diel aidoylphosphatidylethanolamine and it promoted the formation of isotro pic phases in monomethyldioleoylphosphatidylethanolamine. The promotio n 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 b oth decreased the effectiveness of this peptide to induce formation of the hexagonal phase. With the monomethyldioleoylphosphatidylethanolam ine, the fFGOBz also promoted vesicle leakage and fusion as measured b y lipid intermixing. The fFGOBz did not inhibit the formation of lipid structures of high curvature, resulting from sonication of phosphatid ylcholine, as did ZfFG. Thus, the effects of fFGOBz on membranes are i n sharp contrast to those of ZfFG and more closely resemble the behavi our of larger fusion peptides corresponding to the amino-terminal segm ent of viral fusion proteins. Our results demonstrate that having the carbobenzoxy group on the amino-terminus of fFG is important for givin g the peptide derivative the property of inhibiting membrane fusion.