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聚合物纳米盘及其生物分析潜力。

Polymer Nanodiscs and Their Bioanalytical Potential.

机构信息

School of Chemistry, Monash University, Clayton, 3800, Vic, Australia.

出版信息

Chemistry. 2021 Sep 9;27(51):12922-12939. doi: 10.1002/chem.202101572. Epub 2021 Jul 30.

Abstract

Membrane proteins (MPs) play a pivotal role in cellular function and are therefore predominant pharmaceutical targets. Although detailed understanding of MP structure and mechanistic activity is invaluable for rational drug design, challenges are associated with the purification and study of MPs. This review delves into the historical developments that became the prelude to currently available membrane mimetic technologies before shining a spotlight on polymer nanodiscs. These are soluble nanosized particles capable of encompassing MPs embedded in a phospholipid ring. The expanding range of reported amphipathic polymer nanodisc materials is presented and discussed in terms of their tolerance to different solution conditions and their nanodisc properties. Finally, the analytical scope of polymer nanodiscs is considered in both the demonstration of basic nanodisc parameters as well as in the elucidation of structures, lipid-protein interactions, and the functional mechanisms of reconstituted membrane proteins. The final emphasis is given to the unique benefits and applications demonstrated for native nanodiscs accessed through a detergent free process.

摘要

膜蛋白 (MPs) 在细胞功能中起着至关重要的作用,因此是主要的药物靶点。尽管详细了解 MP 的结构和机械活性对于合理的药物设计非常有价值,但在 MPs 的纯化和研究方面仍存在挑战。本文深入探讨了历史发展,这些发展为当前可用的膜模拟技术铺平了道路,然后重点介绍了聚合物纳米盘。这些是可溶性纳米尺寸的颗粒,能够包含嵌入磷脂环中的 MPs。本文介绍并讨论了报道的各种两亲性聚合物纳米盘材料,根据它们对不同溶液条件的耐受性及其纳米盘特性进行了讨论。最后,考虑了聚合物纳米盘的分析范围,包括基本纳米盘参数的演示以及重建的膜蛋白的结构、脂质-蛋白相互作用和功能机制的阐明。最后强调了通过无去污剂过程获得的天然纳米盘所展示的独特优势和应用。

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