Melamine-cored glucosides for membrane protein solubilization and stabilization: importance of water-mediated intermolecular hydrogen bonding in detergent performance

• DOI: 10.1039/d3sc03543c
• Publication Date: 2023-10-23T08:41:15Z
• Authors: Lubna Ghani; Seonghoon Kim; Muhammad Ehsan; Baoliang Lan; Ida H. Poulsen; Chandra Dev; Satoshi Katsube; Bernadette Byrne; Lan Guan; Claus J. Loland; Xiangyu Liu; Wonpil Im; Pil Seok Chae
• Keywords: 570; Chemistry; 540

Membrane proteins play essential roles in a number of biological processes, and their structures are important elucidating such processes at the molecular level also for rational drug design development. protein structure determination is notoriously challenging compared to that soluble proteins, due largely inherent instability non-lipid environments. Micelles formed by conventional detergents have been widely used membrane manipulation, but they suboptimal long-term stability making downstream characterization difficult. Hence, there an unmet need development new amphipathic agents with enhanced efficacy stabilization. In this study, we designed synthesized set glucoside amphiphiles melamine core, denoted melamine-cored glucosides (MGs). When evaluated four (two transporters two G protein-coupled receptors), MG-C11 conferred notably commonly detergents, DDM LMNG. These promising findings mainly attributed unique feature MGs, i.e., ability form dynamic water-mediated hydrogen-bond networks between detergent molecules, as supported dynamics simulations. Thus, first example non-peptide amphiphile capable forming intermolecular hydrogen bonds within protein-detergent complex environment. Detergent micelles via network could represent next generation highly effective membrane-mimetic systems useful structural studies.