Kuyler Gestél C, Barnard Elaine, Sridhar Pooja, Murray Rebecca J, Pollock Naomi L, Wheatley Mark, Dafforn Timothy R, Klumperman Bert
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.
Biomacromolecules. 2025 Jan 13;26(1):415-427. doi: 10.1021/acs.biomac.4c01219. Epub 2024 Dec 26.
Membrane proteins (MPs) are critical to cellular processes and serve as essential therapeutic targets. However, their isolation and characterization are often impeded by traditional detergent-based methods, which can compromise their native states, and retention of their native lipid environment. Amphiphilic polymers have emerged as effective alternatives, enabling the formation of nanoscale discs that preserve MPs' structural and functional integrity. We introduce a novel series of poly(styrene--maleic acid--(-benzyl)maleimide) (BzAM) terpolymers with tunable amphiphilicity, synthesized through controlled polymerization. Designed to mimic and improve upon industry-standard poly(styrene--maleic acid), these well-defined terpolymers offer enhanced control over molecular weight and distribution, allowing for systematic evaluation of polymer properties and their effect on membrane solubilization. The BzAM series effectively solubilized membranes and demonstrated a direct correlation between polymer hydrophobicity and solubilization efficiency of bacterial ABC transporter, Sav1866. This research highlights the importance of rational polymer design in MP research and provides a foundation for future developments.
膜蛋白（MPs）对细胞过程至关重要，是重要的治疗靶点。然而，它们的分离和表征常常受到传统基于洗涤剂的方法的阻碍，这些方法可能会破坏其天然状态以及其天然脂质环境的保留。两亲聚合物已成为有效的替代方法，能够形成保留膜蛋白结构和功能完整性的纳米级圆盘。我们介绍了一系列具有可调两亲性的新型聚（苯乙烯 - 马来酸 - （苄基）马来酰亚胺）（BzAM）三元共聚物，通过可控聚合合成。这些定义明确的三元共聚物旨在模仿并改进行业标准的聚（苯乙烯 - 马来酸），对分子量和分布提供了更强的控制，从而能够系统地评估聚合物性质及其对膜溶解的影响。BzAM系列有效地溶解了膜，并证明了聚合物疏水性与细菌ABC转运蛋白Sav1866的溶解效率之间存在直接关联。这项研究突出了合理聚合物设计在膜蛋白研究中的重要性，并为未来的发展奠定了基础。
