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Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region

Amphiphile selection is a crucial step in membrane protein structural and functional study. As conventional detergents have limited scope and utility, novel agents with enhanced efficacy need to be developed. Although a large number of novel agents have been reported, so far there has been no system...

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Autores principales: Das, Manabendra, Du, Yang, Mortensen, Jonas S., Ribeiro, Orquidea, Hariharan, Parameswaran, Guan, Lan, Loland, Claus J., Kobilka, Brian K., Byrne, Bernadette, Chae, Pil Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369527/
https://www.ncbi.nlm.nih.gov/pubmed/28451257
http://dx.doi.org/10.1039/c6sc02981g
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author Das, Manabendra
Du, Yang
Mortensen, Jonas S.
Ribeiro, Orquidea
Hariharan, Parameswaran
Guan, Lan
Loland, Claus J.
Kobilka, Brian K.
Byrne, Bernadette
Chae, Pil Seok
author_facet Das, Manabendra
Du, Yang
Mortensen, Jonas S.
Ribeiro, Orquidea
Hariharan, Parameswaran
Guan, Lan
Loland, Claus J.
Kobilka, Brian K.
Byrne, Bernadette
Chae, Pil Seok
author_sort Das, Manabendra
collection PubMed
description Amphiphile selection is a crucial step in membrane protein structural and functional study. As conventional detergents have limited scope and utility, novel agents with enhanced efficacy need to be developed. Although a large number of novel agents have been reported, so far there has been no systematically designed comparative study of the protein stabilization efficacy of stereo-isomeric amphiphiles. Here we designed and prepared a novel class of stereo-isomeric amphiphiles, designated butane-1,2,3,4-tetraol-based maltosides (BTMs). These stereoisomers showed markedly different behaviour for most of the targeted membrane proteins depending on the chirality of the linker region. These findings indicate an important role for detergent stereochemistry in membrane protein stabilization. In addition, we generally observed enhanced detergent efficacy with increasing alkyl chain length, reinforcing the importance of the balance between hydrophobicity and hydrophilicity in detergent design. The stereo-isomeric difference in detergent efficacy observed provides an important design principle for the development of novel amphiphiles for membrane protein manipulation.
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spelling pubmed-53695272017-04-27 Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region Das, Manabendra Du, Yang Mortensen, Jonas S. Ribeiro, Orquidea Hariharan, Parameswaran Guan, Lan Loland, Claus J. Kobilka, Brian K. Byrne, Bernadette Chae, Pil Seok Chem Sci Chemistry Amphiphile selection is a crucial step in membrane protein structural and functional study. As conventional detergents have limited scope and utility, novel agents with enhanced efficacy need to be developed. Although a large number of novel agents have been reported, so far there has been no systematically designed comparative study of the protein stabilization efficacy of stereo-isomeric amphiphiles. Here we designed and prepared a novel class of stereo-isomeric amphiphiles, designated butane-1,2,3,4-tetraol-based maltosides (BTMs). These stereoisomers showed markedly different behaviour for most of the targeted membrane proteins depending on the chirality of the linker region. These findings indicate an important role for detergent stereochemistry in membrane protein stabilization. In addition, we generally observed enhanced detergent efficacy with increasing alkyl chain length, reinforcing the importance of the balance between hydrophobicity and hydrophilicity in detergent design. The stereo-isomeric difference in detergent efficacy observed provides an important design principle for the development of novel amphiphiles for membrane protein manipulation. Royal Society of Chemistry 2017-02-01 2016-10-05 /pmc/articles/PMC5369527/ /pubmed/28451257 http://dx.doi.org/10.1039/c6sc02981g Text en This journal is © The Royal Society of Chemistry 2016 http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Das, Manabendra
Du, Yang
Mortensen, Jonas S.
Ribeiro, Orquidea
Hariharan, Parameswaran
Guan, Lan
Loland, Claus J.
Kobilka, Brian K.
Byrne, Bernadette
Chae, Pil Seok
Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
title Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
title_full Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
title_fullStr Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
title_full_unstemmed Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
title_short Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
title_sort butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369527/
https://www.ncbi.nlm.nih.gov/pubmed/28451257
http://dx.doi.org/10.1039/c6sc02981g
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