Gent M P, Prestegard J H
Biochim Biophys Acta. 1976 Feb 19;426(1):17-30. doi: 10.1016/0005-2736(76)90425-9.
The interaction of the polyene antibiotics, amphotericin B, nystatin and filipin with cholesterol-containing single bilayer lipid vesicles has been characterized using gel permeation chromatography and proton magnetic resonance. All three antibiotics bind to vesicles at low concentrations without causing a large amount of vesicle destruction. The strength of binding as determined by gel permeation studies is greater for filipin and amphotericin than for nystatin. Nystatin and amphotericin B at these low concentrations induce a rapid loss of internal vesicle contents consistents consistent with pore formation. Filipin induces no leakage beyond that expected from partial vesicle destruction or general detergent action. At antibiotic levels above 1:1 antibiotic: cholesterol ratios the NMR results show all three antibiotics to cause extensive vesicle destruction. The onset of this behavior, which appears to be independent of the total antibiotic concentraion, indicates a well defined antibiotic : cholesterol interaction stoichiometry. Despite the fact that cholesterol is required for antibiotic activity, the NMR spectra prior to vesicle destruction show no changes indicative of an antibiotic-induced reversal of cholesterol restriction of phosphatidylcholine mobility. The contrast with polyene antibiotic behavior in more extended bilayers is discussed.
利用凝胶渗透色谱法和质子磁共振技术，对多烯抗生素两性霉素B、制霉菌素和菲律宾菌素与含胆固醇的单层脂质囊泡之间的相互作用进行了表征。所有这三种抗生素在低浓度下均能与囊泡结合，且不会导致大量囊泡破坏。通过凝胶渗透研究确定，菲律宾菌素和两性霉素的结合强度大于制霉菌素。在这些低浓度下，制霉菌素和两性霉素B会导致囊泡内物质迅速流失，这与孔形成一致。菲律宾菌素除了因部分囊泡破坏或一般去污剂作用而导致的泄漏外，不会引起额外泄漏。在抗生素与胆固醇的比例高于1:1的抗生素水平下，核磁共振结果表明，所有这三种抗生素都会导致囊泡大量破坏。这种行为的起始似乎与总抗生素浓度无关，这表明存在明确的抗生素与胆固醇相互作用化学计量关系。尽管抗生素活性需要胆固醇，但在囊泡破坏之前的核磁共振谱图未显示出表明抗生素诱导胆固醇对磷脂酰胆碱流动性限制逆转的变化。文中讨论了多烯抗生素在更扩展的双层膜中的行为差异。
