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竹红菌素-胆汁酸缀合物介导的阴离子转运:胆固醇含量的显著影响

Anion Transport by Bambusuril-Bile Acid Conjugates: Drastic Effect of the Cholesterol Content.

作者信息

Torrisi Jacopo, Chvojka Matúš, Jurček Pia, Zhang Xinxin, Zeng Huaqiang, Šindelář Vladimír, Valkenier Hennie

机构信息

Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.

RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.

出版信息

Angew Chem Int Ed Engl. 2025 Feb 24;64(9):e202424754. doi: 10.1002/anie.202424754. Epub 2025 Jan 21.

Abstract

Artificial anion transporters offer a potential way to treat deficiencies in cellular anion transport of genetic origins. In contrast to the large variety of mobile anion carriers and self-assembled anion channels reported, unimolecular anion channels are less investigated. Herein, we present a unique example of a unimolecular anion channel based on a bambusuril (BU) macrocycle, a well-established anion receptor. The BU structure was expanded by appending various bile acid residues allowing a single molecule to span the membrane. Chloride transport mediated by BUs through lipid bilayers was investigated in liposomes and these studies revealed a surprisingly high dependence of the anion transport activity on the cholesterol content in the liposomal membrane.

摘要

人工阴离子转运体为治疗遗传性细胞阴离子转运缺陷提供了一种潜在方法。与报道的种类繁多的可移动阴离子载体和自组装阴离子通道相比,单分子阴离子通道的研究较少。在此,我们展示了一个基于竹节环脲(BU)大环(一种成熟的阴离子受体)的单分子阴离子通道的独特例子。通过连接各种胆汁酸残基扩展了BU结构,使单个分子能够跨越膜。在脂质体中研究了由BU介导的通过脂质双层的氯离子转运,这些研究揭示了阴离子转运活性对脂质体膜中胆固醇含量的惊人高度依赖性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392e/11848992/12aa3dff88f6/ANIE-64-e202424754-g006.jpg

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