Unsymmetric triazine‐based triglucoside detergents for membrane protein stability
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Membrane proteins play a crucial role in a variety of biological processes and are key targets for pharmaceutical development. Structural studies of membrane proteins provide molecular insights into the mechanisms of these processes and are essential for effective drug discovery. Historically, these studies have relied on solubilization of the target protein using detergents, but conventional detergents often fail to maintain the stability of challenging membrane proteins. To address this issue, there is a need to develop novel detergents with enhanced protein stabilization properties. In this study, we synthesized unsymmetric variants of recently reported tris(hydroxymethyl)aminomethane(TRIS)-linker-bearing triazine-based triglucosides (TTGs) by incorporating two different alkyl chains (long and short) into the detergent structure. When tested with model membrane proteins, including a G protein-coupled receptor, TTG-8,12 demonstrated superior efficacy in stabilizing membrane proteins compared to the original TTGs and the gold standard detergents DDM/LMNG. These results suggest that detergent unsymmetry is an important concept for improving detergent performance and unsymmetric detergents such as TTG-8,12 hold significant potential for advancing membrane protein structural studies.
Date Issued
2025-03-03
Date Acceptance
2025-01-03
Citation
ChemBioChem: a European journal of chemical biology, 2025, 26 (5)
ISSN
1439-4227
Publisher
Wiley
Start Page
e202400958
Journal / Book Title
ChemBioChem: a European journal of chemical biology
Volume
26
Issue
5
Copyright Statement
© 2025 Wiley-VCH GmbH. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39779472
Subjects
1,3,5-Triazine
Detergent design
Glucoside detergent
Membrane proteins
Protein stabilization
Detergents
Protein Stability
Triazines
Membrane Proteins
Glucosides
Molecular Structure
Publication Status
Published
Coverage Spatial
Germany
Article Number
e202400958
Date Publish Online
2025-01-28