Diastereomeric Cyclopentane-Based Maltosides (CPMs) as tools for membrane protein study
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Amphiphilic agents, called detergents, are invaluable tools for studying membrane proteins. However, membrane proteins encapsulated by conventional head-to-tail detergents tend to denature or aggregate, necessitating the development of structurally distinct molecules with improved efficacy. Here, a novel class of diastereomeric detergents with a cyclopentane core unit, designated cyclopentane-based maltosides (CPMs), were prepared and evaluated for their ability to solubilize and stabilize several model membrane proteins. A couple of CPMs displayed enhanced behavior compared with the benchmark conventional detergent, n-dodecyl-β-d-maltoside (DDM), for all the tested membrane proteins including two G-protein-coupled receptors (GPCRs). Furthermore, CPM-C12 was notable for its ability to confer enhanced membrane protein stability compared with the previously developed conformationally rigid NBMs [J. Am. Chem. Soc.2017, 139, 3072] and LMNG. The effect of the individual CPMs on protein stability varied depending on both the detergent configuration (cis/trans) and alkyl chain length, allowing us draw conclusions on the detergent structure–property–efficacy relationship. Thus, this study not only provides novel detergent tools useful for membrane protein research but also reports on structural features of the detergents critical for detergent efficacy in stabilizing membrane proteins.
Date Issued
2020-12-23
Date Acceptance
2020-12-01
Citation
Journal of the American Chemical Society, 2020, 142 (51), pp.21382-21392
ISSN
0002-7863
Publisher
American Chemical Society
Start Page
21382
End Page
21392
Journal / Book Title
Journal of the American Chemical Society
Volume
142
Issue
51
Copyright Statement
© 2020 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in J. Am. Chem. Soc., after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jacs.0c09629
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000603395100019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
CRYSTAL-STRUCTURE
BETA(2)-ADRENERGIC RECEPTOR
FACIAL AMPHIPHILES
BILAYER NANODISCS
CRYSTALLIZATION
DETERGENTS
SOLUBILIZATION
STABILIZATION
FLUORESCENCE
EXTRACTION
Publication Status
Published
Date Publish Online
2020-12-14