Das Manabendra, Du Yang, Mortensen Jonas S, Ribeiro Orquidea, Hariharan Parameswaran, Guan Lan, Loland Claus J, Kobilka Brian K, Byrne Bernadette, Chae Pil Seok
Department of Bionanotechnology , Hanyang University , Ansan , 15588 , Korea . Email:
Molecular and Cellular Physiology , Stanford , CA 94305 , USA . Email:
Chem Sci. 2017 Feb 1;8(2):1169-1177. doi: 10.1039/c6sc02981g. Epub 2016 Oct 5.
Amphiphile selection is a crucial step in membrane protein structural and functional study. As conventional detergents have limited scope and utility, novel agents with enhanced efficacy need to be developed. Although a large number of novel agents have been reported, so far there has been no systematically designed comparative study of the protein stabilization efficacy of stereo-isomeric amphiphiles. Here we designed and prepared a novel class of stereo-isomeric amphiphiles, designated butane-1,2,3,4-tetraol-based maltosides (BTMs). These stereoisomers showed markedly different behaviour for most of the targeted membrane proteins depending on the chirality of the linker region. These findings indicate an important role for detergent stereochemistry in membrane protein stabilization. In addition, we generally observed enhanced detergent efficacy with increasing alkyl chain length, reinforcing the importance of the balance between hydrophobicity and hydrophilicity in detergent design. The stereo-isomeric difference in detergent efficacy observed provides an important design principle for the development of novel amphiphiles for membrane protein manipulation.
两亲性分子的选择是膜蛋白结构与功能研究中的关键步骤。由于传统去污剂的范围和效用有限，需要开发具有更高功效的新型试剂。尽管已报道了大量新型试剂，但迄今为止，尚未对立体异构两亲性分子的蛋白质稳定功效进行系统设计的比较研究。在此，我们设计并制备了一类新型立体异构两亲性分子，命名为基于丁烷 -1,2,3,4 -四醇的麦芽糖苷（BTM）。这些立体异构体对大多数靶向膜蛋白表现出明显不同的行为，这取决于连接区域的手性。这些发现表明去污剂立体化学在膜蛋白稳定化中起着重要作用。此外，我们通常观察到随着烷基链长度增加，去污剂功效增强，这强化了去污剂设计中疏水性和亲水性平衡的重要性。所观察到的去污剂功效的立体异构差异为开发用于膜蛋白操作的新型两亲性分子提供了重要的设计原则。
