43 生体膜のイオン透過性を増大させる天然物の分子機構 : 高分解能NMRによる脂質二重膜中の立体配座解析(口頭発表の部)

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Although there are many membrane-active organic compounds including ionophores and channel-forming molecules, the general way to define the conformations of the membrane-bound compounds is not yet established. To address this problem we employed SDS micelles and fast-tumbling bicelles, both of which allow us to measure high-resolution liquid NMR of bound molecules due to their fast reorientation in suspension. We have applied these method to the conformation analyses of amphidinol 3 (AM3) and salinomycin. Salinomycin is a representative ionophore antibiotic. Conformations of salinomycin determined in SDS micelle and bicelle were found to be different. This is possibly attributable to the morphological difference of micelle and bicelle; the former lacks bilayer portion and has high curvature, while the latter is thought to have bilayer structures. Then we investigated the structure of AM3 in membraneous environments. AM3 is a unique dinoflagellate metabolite bearing potent membrane-permeabilizing activity. We previously showed that AM3 forms ion-channel with the inner diameter of 2.0-2.9nm. NMR-constrained modeling experiments in micelle have revealed for the fist time that amphidinols generally take a hairpin configuration, which plausibly account for their potent antifungal and other membrane permeabilizing activities. Conformational study of AM3 in bicelle is now in progress, and the results will be presented.
天然有機化合物討論会の論文
2005-09-15

43 生体膜のイオン透過性を増大させる天然物の分子機構 : 高分解能NMRによる脂質二重膜中の立体配座解析(口頭発表の部)

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