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[甾醇结构在与多烯抗生素形成复合物中的作用]

[Role of sterol structure in complex formation with polyene antibiotics].

作者信息

Feĭgin A M, Belousova I I, Tereshin I M

出版信息

Antibiotiki. 1978 Dec;23(12):1079-83.

PMID:727756
Abstract

The capacity of sterols of different structure being components of artificial bilayer lipid membranes for formation of complexes with polyenic antibiotics, such as amphotericin B, nistatin and levorin was studied. It was shown that sterols delat 5,7-dienic systemin ring B, ergosterol and cholesta-5,7,22-trien 3 beta-ol had the highest affinity to all the 3 antibiotics, while sterols with one double bond in ring B, i. e. cholesterol and brassicasterol had less affinity and sterol without any double bonds in the molecule i.e. 5alpha cholestan 3beta-ol had the least affinity. It was supposed that delta 5,7-sterols had the highest affinity to polyens because of the fact that atoms C-5, C-6; C-7 and C-8 in ring B were practically situated in one plane in contrast to sterols with completely saturated ring B situated in the "conformation chair". Because of this interaction between delta 5,7-sterol ring B and the same flat polyenic site of the antibiotic molecule is sterically most firm since maximum contact is possible between two planes. It was noted that affinity of sterol to the polyenic antibiotics was higher if there were a double bond at 22-23 and methyl group at C-24 in the sterol side chain.

摘要

研究了具有不同结构的甾醇作为人工双层脂质膜成分与多烯抗生素(如两性霉素B、制霉菌素和左菌素)形成复合物的能力。结果表明,在B环中具有δ5,7 - 二烯系统的甾醇、麦角甾醇和胆甾 - 5,7,22 - 三烯 - 3β - 醇对所有这三种抗生素具有最高的亲和力,而在B环中具有一个双键的甾醇,即胆固醇和油菜甾醇的亲和力较低,而分子中没有任何双键的甾醇,即5α - 胆甾烷 - 3β - 醇的亲和力最低。据推测,δ5,7 - 甾醇对多烯具有最高的亲和力,是因为与处于“构象椅”中的完全饱和B环的甾醇相比,B环中的C - 5、C - 6、C - 7和C - 8原子实际上位于同一平面。由于这种δ5,7 - 甾醇B环与抗生素分子相同的扁平多烯位点之间的相互作用在空间上最为牢固,因为两个平面之间可以实现最大程度的接触。值得注意的是,如果甾醇侧链在22 - 23位有一个双键且在C - 24位有一个甲基,则甾醇对多烯抗生素的亲和力更高。

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