Peptide-Scaffolded Detergents for Membrane Protein Studies

作     者：Yang, Meifang Dai, Yili Zhou, Fang Zhou, Xin Qiu, Yanli Tan, Yan Zhao, Suwen Xue, Dongxiang Zhao, Fei Tao, Houchao 

作者机构：Shanghai Univ Tradit Chinese Med Innovat Res Inst Tradit Chinese Med Shanghai Frontiers Sci Ctr TCM Chem Biol Shanghai 201203 Peoples R China Univ South China Inst Pharm & Pharmacol Hengyang Med Sch Hengyang 421001 Hunan Peoples R China ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China 

出 版 物：《CHEMISTRY-A EUROPEAN JOURNAL》 (Chem. Eur. J.)

年 卷 期：2025年第31卷第16期

页      面：e202404520页

核心收录：

学科分类：07[理学] 0703[理学-化学] 

基　　金：NSF of China Shanghai University of Traditional Chinese Medicine ShanghaiTech University 21672147 

主　　题：Peptide-scaffolded detergents Membrane proteins Micelle Click reaction 

摘      要：Detergents are essential for preserving the structural integrity and functionality of membrane proteins (MPs) outside the biological membrane or in aqueous solution, and thus ensuring accurate biochemical and structural analyses. Here, we introduce peptide-scaffolded detergents, a novel class of hybrid molecules formed by preassembling detergent monomers with peptides of varying lengths, mediated via Click chemistry. These detergents are characterized by scalable, straightforward synthesis and enhanced solubility. Among the variants, A4B2 emerged as the optimal detergent, demonstrating superior thermal stabilization across a range of G protein-coupled receptors, including A2AAR, SMO and GLP-1R. Additionally, A4B2 exhibits a low critical micelle concentration and small micelle size, together making it particularly effective for electron microscopy studies of A2AAR. This innovative design leverages the benefits of peptide-based and traditional detergents, offering new insights for the development of advanced detergents in MP research.