Department of Bionanotechnology, Hanyang University, Ansan, 15588, Korea.
Current address: Department of Chemistry, Mirpur University of Science & Technology, Mirpur, AJK, 10250, Pakistan).
Chemistry. 2019 Sep 2;25(49):11545-11554. doi: 10.1002/chem.201902468. Epub 2019 Aug 5.
Amphipathic agents are widely used in various fields including biomedical sciences. Micelle-forming detergents are particularly useful for in vitro membrane-protein characterization. As many conventional detergents are limited in their ability to stabilize membrane proteins, it is necessary to develop novel detergents to facilitate membrane-protein research. In the current study, we developed novel trimaltoside detergents with an alkyl pendant-bearing terphenyl unit as a hydrophobic group, designated terphenyl-cored maltosides (TPMs). We found that the geometry of the detergent hydrophobic group substantially impacts detergent self-assembly behavior, as well as detergent efficacy for membrane-protein stabilization. TPM-Vs, with a bent terphenyl group, were superior to the linear counterparts (TPM-Ls) at stabilizing multiple membrane proteins. The favorable protein stabilization efficacy of these bent TPMs is likely associated with a binding mode with membrane proteins distinct from conventional detergents and facial amphiphiles. When compared to n-dodecyl-β-d-maltoside (DDM), most TPMs were superior or comparable to this gold standard detergent at stabilizing membrane proteins. Notably, TPM-L3 was particularly effective at stabilizing the human β adrenergic receptor (β AR), a G-protein coupled receptor, and its complex with G protein. Thus, the current study not only provides novel detergent tools that are useful for membrane-protein study, but also suggests a critical role for detergent hydrophobic group geometry in governing detergent efficacy.
两亲性试剂广泛应用于包括生物医学科学在内的各个领域。胶束形成洗涤剂对于体外膜蛋白特性分析特别有用。由于许多传统洗涤剂在稳定膜蛋白方面的能力有限，因此有必要开发新型洗涤剂以促进膜蛋白研究。在本研究中，我们开发了一种新型三麦芽糖洗涤剂，其疏水基团为带有烷基侧链的三联苯单元，命名为三联苯核麦芽糖（TPM）。我们发现，洗涤剂疏水基团的几何形状会极大地影响洗涤剂的自组装行为以及稳定膜蛋白的效率。具有弯曲三联苯基团的 TPM-Vs 在稳定多种膜蛋白方面优于线性对应物（TPM-Ls）。这些弯曲 TPM 具有良好的蛋白稳定效果，这可能与其与膜蛋白的结合模式与传统洗涤剂和两亲性表面活性剂不同有关。与正十二烷基-β-D-麦芽糖苷（DDM）相比，大多数 TPM 在稳定膜蛋白方面优于或与该金标准洗涤剂相当。值得注意的是，TPM-L3 特别有效地稳定了人β肾上腺素能受体（βAR），一种 G 蛋白偶联受体及其与 G 蛋白的复合物。因此，本研究不仅提供了新型的洗涤剂工具，可用于膜蛋白研究，还表明了洗涤剂疏水基团几何形状在控制洗涤剂效率方面的重要作用。
