两亲性共聚物及其在膜蛋白研究中的作用。
Amphiphilic Copolymers and Their Role in the Study of Membrane Proteins.
作者信息
Kuyler Gestél C, Barnard Elaine, Cunningham Randy D, Sibariboyi Sinothando, White Luke, Wessels Ilanie, Smith Michael-Phillip, Motloung Bennie, Klumperman Bert
机构信息
Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa.
Centre for Health and Life Sciences, Coventry University, Coventry CV1 2DS, United Kingdom.
出版信息
J Phys Chem Lett. 2025 Jun 12;16(23):5784-5799. doi: 10.1021/acs.jpclett.5c00680. Epub 2025 Jun 3.
Amphiphilic copolymers have revolutionized the study of membrane proteins (MPs), where MPs are known to be critical targets in pharmaceutical development due to their roles in various physiological processes. Traditionally, MP extraction has relied on detergents, which often compromise the protein integrity. Advancements over the past 15 years include the use of poly(styrene--maleic acid) (SMA) to form nanoscale SMALPs (styrene maleic acid lipid particles), enabling detergent-free MP extraction. SMALPs preserve the native environment of MPs, facilitating their detailed analysis through a wide range of biophysical techniques. Despite their advantages, SMA-based technologies face challenges such as sensitivity to divalent cations and instability under low pH conditions. Ongoing research focuses on developing next-generation polymers with enhanced properties, utilizing controlled polymerization techniques to obtain narrow molecular weight distributions and chain-end functionality. This paper explores various SMA derivatives and alternative polymer systems like poly(diisobutylene--maleic acid) (DIBMA) and polymethacrylates, offering potential solutions to current limitations and expanding the toolkit for MP research and application.
两亲性共聚物彻底改变了膜蛋白(MPs)的研究,由于MPs在各种生理过程中的作用,它们在药物开发中是关键靶点。传统上,MP的提取依赖于洗涤剂,这常常会损害蛋白质的完整性。过去15年的进展包括使用聚(苯乙烯-马来酸)(SMA)形成纳米级的SMALPs(苯乙烯马来酸脂质颗粒),实现无洗涤剂的MP提取。SMALPs保留了MPs的天然环境,便于通过广泛的生物物理技术对其进行详细分析。尽管具有优势,但基于SMA的技术面临着诸如对二价阳离子敏感以及在低pH条件下不稳定等挑战。正在进行的研究集中在开发具有增强性能的下一代聚合物,利用可控聚合技术获得窄分子量分布和链端官能团。本文探讨了各种SMA衍生物以及聚(二异丁烯-马来酸)(DIBMA)和聚甲基丙烯酸酯等替代聚合物体系,为当前的局限性提供了潜在的解决方案,并扩展了MP研究和应用的工具包。