1-2-dielaidoylphosphatidylethanolamine and carbobenzoxyphenylalanyl-phenylalanyl-glycine

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.

Topics: Amino Acid Sequence; Calorimetry, Differential Scanning; Hydrogen-Ion Concentration; Lipid Bilayers; Magnetic Resonance Spectroscopy; Membrane Fusion; Models, Biological; Molecular Sequence Data; Oligopeptides; Phosphatidylethanolamines; Sonication; Temperature; Viral Fusion Proteins

Virus replication inhibitory peptide (carbobenzoxy-D-Phe-L-PheGly) was shown to be a potent specific inhibitor of the replication of paramyxovirus and myxovirus (Richardson, Scheid and Choppin (1980), Virology 105, 205-222). This peptide inhibits the membrane fusing activity of a viral glycoprotein. Many agents which promote the formation of the hexagonal phase in membranes also accelerate membrane fusion. At a mole fraction of 0.1, viral replication inhibitory peptide can raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine by almost 10 degrees. Two related peptides, carbobenzoxy-L-PheGly and carbobenzoxy-L-GlyPhe, are less potent in raising the bilayer to hexagonal phase transition temperature, with the latter peptide being the least effective of the three. This order of potency is the same as the order of potency in inhibiting viral replication. Substances which inhibit hexagonal phase formation of pure lipids may also inhibit membrane fusion.

Topics: Calorimetry, Differential Scanning; Dipeptides; Lipid Bilayers; Molecular Conformation; Oligopeptides; Phosphatidylethanolamines; Structure-Activity Relationship