Effects of viral chemotherapeutic agents on membrane properties. Studies of cyclosporin A, benzyloxycarbonyl-D-Phe-L-Phe-Gly and amantadine.
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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.
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