Multiple pendants-bearing triglucosides for membrane protein studies: effects of pendant length and number on micelle interior hydration and protein stability
File(s) MPG Sym.pdf (2.22 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Membrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic–lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β2AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research.
Date Issued
2025-04-14
Date Acceptance
2025-03-07
Citation
Biomacromolecules, 2025, 26 (4), pp.2565-2579
ISSN
1525-7797
Publisher
American Chemical Society
Start Page
2565
End Page
2579
Journal / Book Title
Biomacromolecules
Volume
26
Issue
4
Copyright Statement
Copyright © 2025 American Chemical Society. 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/40087026
Subjects
Micelles
Glucosides
Protein Stability
Humans
Molecular Dynamics Simulation
Hydrophobic and Hydrophilic Interactions
Detergents
Water
Membrane Proteins
Receptors, Adrenergic, beta-2
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-03-14
