Tris(hydroxymethyl)aminomethane linker-bearing triazine-based triglucosides for solubilization and stabilization of membrane proteins
File(s)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2023-04-19
Date Acceptance
2023-03-01
Citation
Bioconjugate Chemistry, 2023, 34 (4), pp.739-747
ISSN
1043-1802
Publisher
American Chemical Society
Start Page
739
End Page
747
Journal / Book Title
Bioconjugate Chemistry
Volume
34
Issue
4
Copyright Statement
Copyright © 2023 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate Chem., after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.bioconjchem.3c00042
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000973026200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
BETA(2)-ADRENERGIC RECEPTOR
BINDING
Biochemical Research Methods
Biochemistry & Molecular Biology
Chemistry
Chemistry, Multidisciplinary
Chemistry, Organic
CONFORMATION
CRYSTAL
DETERGENTS
FLUORESCENCE
GENOME
GNG AMPHIPHILES
IMPACT
INSIGHTS
Life Sciences & Biomedicine
Physical Sciences
Science & Technology
Publication Status
Published
Date Publish Online
2023-03-15