Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region.
Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region.
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DOI：
10.1039/c6sc02981g
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发表时间：
2017-02-01
期刊：
影响因子：
8.4
通讯作者：
Chae PS
中科院分区：
文献类型：
--
作者：
Das M;Du Y;Mortensen JS;Ribeiro O;Hariharan P;Guan L;Loland CJ;Kobilka BK;Byrne B;Chae PS
两亲性结构的手性变化导致洗涤剂对膜蛋白稳定的效果有显著差异。两亲性选择是膜蛋白结构和功能研究中的关键步骤。由于常规洗涤剂的使用范围和用途有限，需要开发新的高效洗涤剂。虽然已经报道了大量的新型试剂，但到目前为止还没有系统的设计比较研究立体异构体两亲分子的蛋白质稳定效果。本文设计并合成了一类新型的立体异构体两亲化合物，命名为丁烷-1，2，3，4-四醇麦芽糖苷(BTMS)。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，这取决于连接区的手性。这些发现表明了洗涤剂立体化学在膜蛋白稳定中的重要作用。此外，我们普遍观察到，随着烷基链长的增加，洗涤剂的功效增强，这加强了疏水性和亲水性之间的平衡在洗涤剂设计中的重要性。观察到的洗涤剂功效的立体异构体差异为开发新型两亲性膜蛋白操纵剂提供了重要的设计原则。
Chirality variation in amphiphile architecture resulted in a significant difference in detergent efficacy for membrane protein stabilisation. 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.