On the mechanism of inhibition of viral and vesicle membrane fusion by carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine.
The mechanism by which the hydrophobic peptide Z-D-Phe-L-PheGly inhibits membrane fusion was investigated. Differential scanning calorimetry, 2H nuclear magnetic resonance (NMR), and 13C NMR of phosphatidylcholine bilayers in the presence of Z-D-Phe-L-PheGly indicate that this hydrophobic peptide penetrates the phospholipid bilayer but does not strongly perturb the properties of phosphatidylcholine bilayers with a large effective radius of curvature. However, Z-D-Phe-L-PheGly does affect the properties of highly curved phosphatidylcholine bilayers. Small, sonicated vesicles (SUV) of dipalmitoylphosphatidylcholine (DPPC) were made in the presence and absence of Z-D-Phe-L-PheGly. At pH 4.5, the presence of Z-D-Phe-L-PheGly inhibited the formation of SUV. At pH 6.7 and 7.4, SUV could form. Once sonication ceased and the vesicles were incubated at 23 degrees C, modest growth in vesicle size occurred for pure DPPC SUV. Rapid change to large sheetlike structures occurred in the presence of Z-D-Phe-L-PheGly. Z-D-Phe-L-PheGly appeared to favor the formation of phospholipid structures with large radii of curvature. In these experiments, Z-D-Phe-L-PheGly had access to both sides of the bilayer. If Z-D-Phe-L-PheGly was added to preformed DPPC SUV (and thus present initially only in the outer leaflet of the vesicle bilayer) and incubated at 23 degrees C, only modest growth in vesicle size was observed with little difference from control values at short to intermediate incubation times.(ABSTRACT TRUNCATED AT 250 WORDS)
Yeagle
P L
PL
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
Young
J
J
Hui
S W
SW
Epand
R M
RM
D015060:1,2-Dipalmitoylphosphatidylcholine; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry*
D000998:Antiviral Agents; D008051:Lipid Bilayers; D009842:Oligopeptides; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; C050811:carbobenzoxyphenylalanyl-phenylalanyl-glycine