Molecular organization, localization and orientation of antifungal antibiotic amphotericin B in a single lipid bilayer.
Molecular organization, localization and orientation of antifungal antibiotic amphotericin B in a single lipid bilayer.
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DOI：
10.1038/srep32780
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发表时间：
2016-09-13
影响因子：
4.6
通讯作者：
Gruszecki WI
中科院分区：
文献类型：
--
作者：
Grudzinski W;Sagan J;Welc R;Luchowski R;Gruszecki WI
两性霉素B是一种广受欢迎的抗真菌抗生素，因其高效而成为治疗系统性真菌感染的黄金标准。另一方面，该药物的适用性因其对患者的相当大的毒性而受到限制。生物膜是两性霉素B生理活性的主要靶点，药物的药理作用和毒副作用都依赖于它在脂类阶段的分子组织。利用共聚焦荧光寿命成像显微镜研究了两性霉素B在单脂双层体系中的分子组成、定位和取向。结果表明，在脂相中，甾醇的存在促进了两性霉素B超分子结构的形成和膜疏水核心的渗透。事实上，在胆固醇的情况下，这种影响比真菌膜上的甾醇麦角甾醇要小得多，这一事实为药物的选择性提供了分子洞察力。
Amphotericin B is a popular antifungal antibiotic, a gold standard in treatment of systemic mycotic infections, due to its high effectiveness. On the other hand, applicability of the drug is limited by its considerable toxicity to patients. Biomembranes are a primary target of physiological activity of amphotericin B and both the pharmacologically desired and toxic side effects of the drug relay on its molecular organization in the lipid phase. In the present work, molecular organization, localization and orientation of amphotericin B, in a single lipid bilayer system, was analysed simultaneously, thanks to application of a confocal fluorescence lifetime imaging microscopy of giant unilamellar vesicles. The results show that the presence of sterols, in the lipid phase, promotes formation of supramolecular structures of amphotericin B and their penetration into the membrane hydrophobic core. The fact that such an effect is substantially less pronounced in the case of cholesterol than ergosterol, the sterol of fungal membranes, provides molecular insight into the selectivity of the drug.
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影响因子：
14.8
作者：
Anderson TM;Clay MC;Cioffi AG;Diaz KA;Hisao GS;Tuttle MD;Nieuwkoop AJ;Comellas G;Maryum N;Wang S;Uno BE;Wildeman EL;Gonen T;Rienstra CM;Burke MD
通讯作者：
Burke MD
DOI：
10.1016/0005-2736(90)90133-9
发表时间：
1990-04-30
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GRUSZECKI, WI;SIELEWIESIUK, J
通讯作者：
SIELEWIESIUK, J
影响因子：
3.9
作者：
Neumann, Anna;Wieczor, Milosz;Czub, Jacek
通讯作者：
Czub, Jacek
影响因子：
158.5
作者：
Mora-Duarte, J;Betts, R;Perfect, J
通讯作者：
Perfect, J
影响因子：
5.8
作者：
Herec, M;Dziubinska, H;Gruszecki, WI
通讯作者：
Gruszecki, WI