1,3,5-Triazine-Cored Maltoside Amphiphiles for Membrane Protein Extraction and Stabilization
1,3,5-Triazine-Cored Maltoside Amphiphiles for Membrane Protein Extraction and Stabilization
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DOI：
10.1021/jacs.9b07883
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发表时间：
2019-12-18
影响因子：
15
通讯作者：
Chae, Pil Seok
中科院分区：
文献类型：
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作者：
Ghani, Lubna;Munk, Chastine F.;Chae, Pil Seok
尽管膜蛋白具有重要的生物学和药理学意义，但其结构和功能的研究仍然是一个重大挑战。一个主要问题是从天然脂质膜中分离出稳定和功能状态的这些蛋白质。洗涤剂是一种两亲性化合物，广泛用于从天然膜中提取膜蛋白，并在下游分析过程中保持其稳定形式。然而，由于传统洗涤剂的局限性，开发具有最佳蛋白质稳定性的新型两亲体对于推进膜蛋白的研究至关重要。本文设计并合成了以三聚氰尿酸为原料的1,3,5-三嗪为核心的二麦芽糖苷两亲体。通过引入烷基链连接的变化（醚/硫醚）和胺功能化的二醇连接（丝氨酸醇/二乙醇胺），我们制备了两套1,3,5-三嗪基洗涤剂。当与几种模型膜蛋白进行测试时，这些药物在稳定三种转运蛋白和两种G蛋白偶联受体方面表现出显著的功效。洗涤剂的行为根据洗涤剂结构的变化而变化，这使我们能够探索洗涤剂结构-性能-功效的关系。本文介绍的1,3,5-三嗪基洗涤剂由于其结构多样性和对几种膜蛋白的普遍稳定作用，在膜蛋白研究中具有重要的潜力。
Despite their major biological and pharmacological significance, the structural and functional study of membrane proteins remains a significant challenge. A main issue is the isolation of these proteins in a stable and functional state from native lipid membranes. Detergents are amphiphilic compounds widely used to extract membrane proteins from the native membranes and maintain them in a stable form during downstream analysis. However, due to limitations of conventional detergents, it is essential to develop novel amphiphiles with optimal properties for protein stability in order to advance membrane protein research. Here we designed and synthesized 1,3,5-triazine-cored dimaltoside amphiphiles derived from cyanuric chloride. By introducing variations in the alkyl chain linkage (ether/thioether) and an amine-functionalized diol linker (serinol/diethanolamine), we prepared two sets of 1,3,5-triazine-based detergents. When tested with several model membrane proteins, these agents showed remarkable efficacy in stabilizing three transporters and two G protein-coupled receptors. Detergent behavior substantially varied depending on the detergent structural variation, allowing us to explore detergent structure-property-efficacy relationships. The 1,3,5-triazine-based detergents introduced here have significant potential for membrane protein study as a consequence of their structural diversity and universal stabilization efficacy for several membrane proteins.