Molecular basis of glycoalkaloid induced membrane disruption
Molecular basis of glycoalkaloid induced membrane disruption
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DOI：
10.1016/0005-2736(95)00186-7
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发表时间：
1995-12-13
影响因子：
3.4
通讯作者：
deKruijff, B
中科院分区：
文献类型：
--
作者：
Keukens, EAJ;deVrije, T;deKruijff, B
在这项研究中，利用膜渗漏、结合实验、去污剂萃取、电子显微镜、核磁共振和分子建模等技术，系统地分析了模型膜中配糖生物碱α-卡茄碱、α-茄碱和α-番茄碱与甾醇之间的相互作用。甾醇与配糖生物碱相互作用的最重要特性是平面环结构和 3 β-OH 基团，而对于 α-查茄碱，5-6 双键和 10-甲基基团也很重要。 α-查茄碱和α-茄碱之间的高度协同效应、糖脂的渗漏增强作用以及从配糖生物碱中删除一种或多种单糖后几乎完全丧失活性，说明了糖-糖相互作用的重要性。所形成的复合物对洗涤剂提取具有抗性，配糖生物碱/甾醇以 1:1 的比例存在，并形成具有内部单层磷脂的管状结构（α-查茄碱），而与 α-番茄碱也形成球形结构。基于结果，提出了配糖生物碱诱导的膜破坏的分子模型。
In this study the interaction between the glycoalkaloids alpha-chaconine, alpha-solanine and alpha-tomatine and sterols in model membranes was analysed systematically using techniques like membrane leakage, binding experiments, detergent extraction, electron microscopy, NMR and molecular modelling. The most important properties for sterols to interact with glycoalkaloids turned out to be a planar ring structure and a 3 beta-OH group, whereas for alpha-chaconine the 5-6 double bond and the 10-methyl group were also of importance. The importance of sugar-sugar interactions was illustrated by the high synergistic effect between alpha-chaconine and alpha-solanine, the leakage enhancing effect of glycolipids, and the almost complete loss of activity after deleting one or more mono-saccharides from the glycoalkaloids. The formed complexes which were resistant against detergent extraction existed of glycoalkaloid/sterol in a 1:1 ratio and formed tubular structures (alpha-chaconine) with an inner monolayer of phospholipids, whereas with alpha-tomatine also spherical structures were formed, Based on the results a molecular model for glycoalkaloid induced membrane disruption is presented.