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J. Biol. Chem., Vol. 262, Issue 4, 1526-1529, 02, 1987
RM Epand, RF Epand and RC McKenzie
Cyclosporin A, benzyloxycarbonyl-D-Phe-L-Phe-Gly, and amantadine inhibit
the dilution of fluorescently labeled lipids, as measured with the
resonance energy exchange assay for membrane fusion. The fusion was studied
using sonicated vesicles containing 1,2-dioleoyl-sn-
glycero(3)phosphoethanolamine, egg (3-sn-phosphatidyl)choline, and
cholesterol in a 1:1:1.3 molar ratio. All three antiviral agents inhibited
myelin basic protein-induced membrane fusion when present at low
concentrations in the membrane. The mechanism by which these agents affect
membrane properties was investigated. The effect of these agents on the
bilayer to hexagonal phase transition of 1,2-dielaidoyl-sn-
glycero(3)phosphoethanolamine was determined using both differential
scanning calorimetry and 31P NMR. Benzyloxycarbonyl-D-Phe-L-Phe-Gly is
particularly effective in raising the bilayer to hexagonal phase transition
temperature while cyclosporin promotes the greatest amount of broadening of
the 31P NMR signal. Both effects are suggested to be related to the
inhibitory activity of these substances on membrane fusion and possibly
also to their antiviral activity.
Effects of viral chemotherapeutic agents on membrane properties. Studies of cyclosporin A, benzyloxycarbonyl-D-Phe-L-Phe-Gly and amantadine
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