Unique aggregation of conjugated amphotericin B and its interaction with lipid membranes
Unique aggregation of conjugated amphotericin B and its interaction with lipid membranes
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结合两性霉素 B 的独特聚集及其与脂膜的相互作用
DOI：
10.1093/mmy/myw099
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
I. Polacheck
中科院分区：
文献类型：
--
作者：
S. Kagan;D. Ickowicz;A. Domb;A. Dagan;I. Polacheck
摘要 本文的目的是研究两性霉素 B (AMB) 和 AMB-阿拉伯半乳聚糖缀合物 (AMB-AGC) 的聚集，以及这些药物与游离甾醇和膜嵌入甾醇的相互作用。通过圆二色性 (CD) 和紫外吸收光谱技术研究了 AMB 和 AMB-AGC 的聚集。利用脂质体对光谱的影响来研究聚集体与膜嵌入的甾醇的相互作用。通过测量甾醇对 AMB/AMB-AGC 药敏试验的影响来研究与游离甾醇的相互作用。结果表明，AMB-AGC 在水溶液中形成独特的聚集体，与游离 AMB 形成的聚集体不同。脂质体中嵌入的麦角甾醇和胆固醇影响了 AMB 和 AMB-AGC 获得的圆二色光谱，表明这些甾醇与这两种药物存在相互作用。与胆固醇和麦角甾醇的相互作用导致 AMB-AGC 对白色念珠菌的最小抑制浓度 (MIC) 增加。总之，AMB-AGC 在水溶液中形成独特的聚集体；这些聚集体与膜嵌入的胆固醇和麦角甾醇以及游离甾醇相互作用。这些结果表明，AMB-AGC 对真菌细胞的选择性可能不是由于无法结合胆固醇而发生，而是可能是这种独特聚集的结果。了解这一机制可能有助于开发更安全的 AMB 治疗制剂。
Abstract The purpose of this paper was to investigate the aggregation of amphotericin B (AMB) and AMB‐arabinogalactan conjugate (AMB‐AGC), and the interactions of these drugs with free and membrane‐embedded sterols. Aggregation of AMB and AMB‐AGC was studied by circular dichroic (CD) and UV absorbance spectroscopic techniques. The effect of liposomes on the spectra was utilized to investigate the interactions of aggregates with membrane‐embedded sterols. Interaction with free sterols was studied by measuring sterols' effect on AMB/AMB‐AGC susceptibility test. The results demonstrated that AMB‐AGC forms unique aggregates in aqueous solution which differ from those formed by free AMB. Ergosterol and cholesterol embedded in liposomes, affected the CD spectra obtained for both AMB and AMB‐AGC, indicating interactions of these sterols with both drugs. Interaction with both cholesterol and ergosterol resulted in an increase of AMB‐AGC's minimal inhibitory concentration (MIC) in Candida albicans. In conclusion, AMB‐AGC forms unique aggregates in aqueous solution; these aggregates interact with membrane‐embedded cholesterol and ergosterol and with free sterols. These results indicate that the selectivity of AMB‐AGC to fungal cells may not occur due to inability to bind cholesterol but probably as a result of this unique aggregation. Understanding this mechanism may help to develop a safer AMB formulation for therapy.
影响因子：
15
作者：
Wilcock, Brandon C.;Endo, Matthew M.;Uno, Brice E.;Burke, Martin D.
通讯作者：
Burke, Martin D.