Tris(hydroxymethyl)aminomethane Linker-Bearing Triazine-Based Triglucosides for Solubilization and Stabilization of Membrane Proteins

Lubna Ghani, Xiang Zhang, Chastine F. Munk, Parameswaran Hariharan, Baoliang Lan, Hong Sik Yun, Bernadette Byrne, Lan Guan, Claus J. Loland, Xiangyu Liu, Pil Seok Chae*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

3 Citations (Scopus)

Abstract

High-resolution membrane protein structures are essential for a fundamental understanding of the molecular basis of diverse cellular processes and for drug discovery. Detergents are widely used to extract membrane-spanning proteins from membranes and maintain them in a functional state for downstream characterization. Due to limited long-term stability of membrane proteins encapsulated in conventional detergents, development of novel agents is required to facilitate membrane protein structural study. In the current study, we designed and synthesized tris(hydroxymethyl)aminomethane linker-bearing triazine-based triglucosides (TTGs) for solubilization and stabilization of membrane proteins. When these glucoside detergents were evaluated for four membrane proteins including two G protein-coupled receptors, a few TTGs including TTG-C10 and TTG-C11 displayed markedly enhanced behaviors toward membrane protein stability relative to two maltoside detergents [DDM (n-dodecyl-β-d-maltoside) and LMNG (lauryl maltose neopentyl glycol)]. This is a notable feature of the TTGs as glucoside detergents tend to be inferior to maltoside detergents at stabilizing membrane proteins. The favorable behavior of the TTGs for membrane protein stability is likely due to the high hydrophobicity of the lipophilic groups, an optimal range of hydrophilic-lipophilic balance, and the absence of cis-trans isomerism.

Original languageEnglish
JournalBioconjugate Chemistry
Volume34
Issue number4
Number of pages9
ISSN1043-1802
DOIs
Publication statusPublished - 2023

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