Tailoring butane-1,2,3,4-tetraol-based maltosides (BTMs) via group-swapping and detergent unsymmetry: new detergent design strategies for membrane protein studies
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Membrane proteins are essential bio-macromolecules involved in numerous critical biological processes and serve as therapeutic targets for a wide range of modern pharmaceuticals. Small amphipathic molecules, called detergents or surfactants, are widely used for the isolation and structural characterization of these proteins. A key requirement for such studies is their ability to maintain membrane protein stability in aqueous solution, a task where conventional detergents often fall short. While many new detergents have been developed based on novel molecular scaffolds, comparatively little effort has been made to enhance detergent performance through rational modification of existing structures, largely due to the limited availability of guiding design principles and strategies. In this study, we refined previously developed butane-1,2,3,4-tetraol based maltosides (BTMs), using two structural modification strategies, head/tail group-swapping and the introduction of hydrophobic unsymmetry. The resulting group-swapped (GS)-BTMs exhibited distinctive physical properties compared to the original BTM, including differences in water-solubility (∼7 to >10 wt%), critical aggregation concentration (5 to 15 μM), and self-assembly size (7.6 to 34.2 nm). When evaluated using model membrane proteins, including the human adrenergic receptor (β2AR), symmetric GS-BTMs (e.g., GS-BTM-C11 and GS-BTM-C12) showed superior performance relative to the original BTM-C11 and benchmark detergents (DDM and LMNG). The unsymmetric variants, such as GS-BTM-C14,10 and GS-BTM-C15,9, further improved protein stability. These findings highlight group-swapping and hydrophobic unsymmetry as effective strategies for enhancing detergent performance. This work demonstrates how minimal structural modifications can impact detergent properties and efficacy, providing valuable insights for the development of improved detergents from existing molecular frameworks.
Date Issued
2025-08-20
Date Acceptance
2025-08-18
Citation
Journal of Materials Chemistry B, 2025, 13 (39), pp.12569-12578
ISSN
2050-750X
Publisher
Royal Society of Chemistry
Start Page
12569
End Page
12578
Journal / Book Title
Journal of Materials Chemistry B
Volume
13
Issue
39
Copyright Statement
This journal is © The Royal Society of Chemistry 2025. 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/40916887
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-08-20