Tandem Malonate-based Glucosides (TMGs) for Membrane Protein Structural Studies

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jun 23

PMID 28638082

Citations 5

Authors

Hazrat Hussain

Jonas S Mortensen

Yang Du

Claudia Santillan

Orquidea Ribeiro

Juyeon Go

Parameswaran Hariharan

Claus J Loland

Lan Guan

Brian K Kobilka

Bernadette Byrne

Pil Seok Chae

Affiliations

Soon will be listed here.

Abstract

High-resolution membrane protein structures are essential for understanding the molecular basis of diverse biological events and important in drug development. Detergents are usually used to extract these bio-macromolecules from the membranes and maintain them in a soluble and stable state in aqueous solutions for downstream characterization. However, many eukaryotic membrane proteins solubilized in conventional detergents tend to undergo structural degradation, necessitating the development of new amphiphilic agents with enhanced properties. In this study, we designed and synthesized a novel class of glucoside amphiphiles, designated tandem malonate-based glucosides (TMGs). A few TMG agents proved effective at both stabilizing a range of membrane proteins and extracting proteins from the membrane environment. These favourable characteristics, along with synthetic convenience, indicate that these agents have potential in membrane protein research.

Citing Articles

Rational Approach to Improve Detergent Efficacy for Membrane Protein Stabilization.

Yoon S, Bae H, Hariharan P, Nygaard A, Lan B, Woubshete M Bioconjug Chem. 2024; 35(2):223-231.

PMID: 38215010 PMC: 10970486. DOI: 10.1021/acs.bioconjchem.3c00507.

Foldable Detergents for Membrane Protein Study: Importance of Detergent Core Flexibility in Protein Stabilization.

Ghani L, Kim S, Wang H, Lee H, Mortensen J, Katsube S Chemistry. 2022; 28(21):e202200116.

PMID: 35238091 PMC: 9007890. DOI: 10.1002/chem.202200116.

Diastereomeric Cyclopentane-Based Maltosides (CPMs) as Tools for Membrane Protein Study.

Das M, Mahler F, Hariharan P, Wang H, Du Y, Mortensen J J Am Chem Soc. 2020; 142(51):21382-21392.

PMID: 33315387 PMC: 8015409. DOI: 10.1021/jacs.0c09629.

Steroid-Based Amphiphiles for Membrane Protein Study: The Importance of Alkyl Spacers for Protein Stability.

Ehsan M, Das M, Stern V, Du Y, Mortensen J, Hariharan P Chembiochem. 2018; 19(13):1433-1443.

PMID: 29660780 PMC: 7238963. DOI: 10.1002/cbic.201800106.

Thermodynamic cooperativity of cosubstrate binding and cation selectivity of MelB.

Hariharan P, Guan L J Gen Physiol. 2017; 149(11):1029-1039.

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