4
IRUS Total
Downloads
  Altmetric

1,3,5-Triazine-cored maltoside amphiphiles for membrane protein extraction and stabilization

File Description SizeFormat 
TSM_TEM_ms_Accepted.docxAccepted version9.5 MBMicrosoft WordView/Open
Title: 1,3,5-Triazine-cored maltoside amphiphiles for membrane protein extraction and stabilization
Authors: Ghani, L
Munk, CF
Zhang, X
Katsube, S
Du, Y
Cecchetti, C
Huang, W
Bae, HE
Saouros, S
Ehsan, M
Guan, L
Liu, X
Loland, CJ
Kobilka, BK
Byrne, B
Chae, PS
Item Type: Journal Article
Abstract: Despite their major biological and pharmacological significance, the structural and functional study of membrane proteins remains a significant challenge. A main issue is the isolation of these proteins in a stable and functional state from native lipid membranes. Detergents are amphiphilic compounds widely used to extract membrane proteins from the native membranes and maintain them in a stable form during downstream analysis. However, due to limitations of conventional detergents, it is essential to develop novel amphiphiles with optimal properties for protein stability in order to advance membrane protein research. Here we designed and synthesized 1,3,5-triazine-cored dimaltoside amphiphiles derived from cyanuric chloride. By introducing variations in the alkyl chain linkage (ether/thioether) and an amine-functionalized diol linker (serinol/diethanolamine), we prepared two sets of 1,3,5-triazine-based detergents. When tested with several model membrane proteins, these agents showed remarkable efficacy in stabilizing three transporters and two G protein-coupled receptors. Detergent behavior substantially varied depending on the detergent structural variation, allowing us to explore detergent structure–property–efficacy relationships. The 1,3,5-triazine-based detergents introduced here have significant potential for membrane protein study as a consequence of their structural diversity and universal stabilization efficacy for several membrane proteins.
Issue Date: 18-Dec-2019
Date of Acceptance: 23-Nov-2019
URI: http://hdl.handle.net/10044/1/76787
DOI: 10.1021/jacs.9b07883
ISSN: 0002-7863
Publisher: American Chemical Society
Start Page: 19677
End Page: 19687
Journal / Book Title: Journal of the American Chemical Society
Volume: 141
Issue: 50
Copyright Statement: © 2019 American Chemical Society
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
CRYSTAL-STRUCTURE
STRUCTURAL INSIGHTS
FACIAL AMPHIPHILES
DETERGENT
RECEPTOR
CRYSTALLIZATION
SOLUBILIZATION
FLUORESCENCE
AMPHIPOLS
ANALOGS
Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
CRYSTAL-STRUCTURE
STRUCTURAL INSIGHTS
FACIAL AMPHIPHILES
DETERGENT
RECEPTOR
CRYSTALLIZATION
SOLUBILIZATION
FLUORESCENCE
AMPHIPOLS
ANALOGS
General Chemistry
03 Chemical Sciences
Publication Status: Published
Online Publication Date: 2019-12-06
Appears in Collections:Faculty of Natural Sciences