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多烯抗生素与膜脂的相互作用:选择性分子基础的物理化学研究

Interaction of polyene antibiotics with membrane lipids: physicochemical studies of the molecular basis of selectivity.

作者信息

Bolard J

出版信息

Drugs Exp Clin Res. 1986;12(6-7):613-8.

PMID:3527632
Abstract

From various studies on the interaction of amphotericin B with unilamellar lipid vesicles, it appears that the strength of the binding does not depend only on the presence of sterol molecules in the membranes; and that several bound amphotericin B species are in competition, their relative amounts depending on the nature and percentage of sterol in the lipid bilayer. Bound amphotericin B molecules exchange rapidly between the membranes. It is therefore possible to add the antibiotic by transfer from amphotericin B-preloaded vesicles of dipalmitoylphosphatidylcholine, instead of direct addition. In these conditions the selectivity in the sensitivity to H+ leakage induced by amphotericin B between ergosterol- and cholesterol-containing vesicles is greatly enhanced. In the case of Mycoplasma laidlawii cells, a preliminary increase of K+ cellular content is observed when low doses of amphotericin B are added by transfer, an effect which is not observed with direct addition of the antibiotic.

摘要

通过对两性霉素B与单层脂质囊泡相互作用的各种研究表明,结合强度不仅取决于膜中固醇分子的存在;而且几种结合的两性霉素B物种相互竞争,它们的相对含量取决于脂质双层中固醇的性质和百分比。结合的两性霉素B分子在膜之间快速交换。因此,可以通过从预先装载两性霉素B的二棕榈酰磷脂酰胆碱囊泡转移来添加抗生素,而不是直接添加。在这些条件下,两性霉素B诱导的含麦角固醇和含胆固醇囊泡对H+泄漏敏感性的选择性大大增强。在莱氏无胆甾原体细胞的情况下,当通过转移添加低剂量的两性霉素B时,观察到细胞内K+含量初步增加,而直接添加抗生素时未观察到这种效果。

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