Maltose-bis(hydroxymethyl)phenol (MBPs) and Maltose-tris(hydroxymethyl)phenol (MTPs) Amphiphiles for Membrane Protein Stability
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Maltose-bis(hydroxymethyl)phenol (MBPs) and Maltose-tris(hydroxymethyl)phenol (MTPs) Amphiphiles for Membrane Protein Stability. / Ehsan, Muhammad; Wang, Haoqing; Cecchetti, Cristina; Mortensen, Jonas S.; Du, Yang; Hariharan, Parameswaran; Nygaard, Andreas; Lee, Ho Jin; Ghani, Lubna; Guan, Lan; Loland, Claus J.; Byrne, Bernadette; Kobilka, Brian K.; Chae, Pil Seok.
In: ACS chemical biology, Vol. 16, No. 9, 2021, p. 1779–1790.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Maltose-bis(hydroxymethyl)phenol (MBPs) and Maltose-tris(hydroxymethyl)phenol (MTPs) Amphiphiles for Membrane Protein Stability
AU - Ehsan, Muhammad
AU - Wang, Haoqing
AU - Cecchetti, Cristina
AU - Mortensen, Jonas S.
AU - Du, Yang
AU - Hariharan, Parameswaran
AU - Nygaard, Andreas
AU - Lee, Ho Jin
AU - Ghani, Lubna
AU - Guan, Lan
AU - Loland, Claus J.
AU - Byrne, Bernadette
AU - Kobilka, Brian K.
AU - Chae, Pil Seok
N1 - Publisher Copyright: © 2021 American Chemical Society.
PY - 2021
Y1 - 2021
N2 - Membrane protein structures provide a fundamental understanding of their molecular actions and are of importance for drug development. Detergents are widely used to solubilize, stabilize, and crystallize membrane proteins, but membrane proteins solubilized in conventional detergents are prone to denaturation and aggregation. Thus, developing novel detergents with enhanced efficacy for protein stabilization remains important. We report herein the design and synthesis of a class of phenol-derived maltoside detergents. Using two different linkers, we prepared two sets of new detergents, designated maltose-bis(hydroxymethyl)phenol (MBPs) and maltose-tris(hydroxymethyl)phenol (MTPs). The evaluation of these detergents with three transporters and two G-protein coupled receptors allowed us to identify a couple of new detergents (MBP-C9 and MTP-C12) that consistently conferred enhanced stability to all tested proteins compared to a gold standard detergent (DDM). Furthermore, the data analysis based on the detergent structures provides key detergent features responsible for membrane protein stabilization that together will facilitate the future design of novel detergents.
AB - Membrane protein structures provide a fundamental understanding of their molecular actions and are of importance for drug development. Detergents are widely used to solubilize, stabilize, and crystallize membrane proteins, but membrane proteins solubilized in conventional detergents are prone to denaturation and aggregation. Thus, developing novel detergents with enhanced efficacy for protein stabilization remains important. We report herein the design and synthesis of a class of phenol-derived maltoside detergents. Using two different linkers, we prepared two sets of new detergents, designated maltose-bis(hydroxymethyl)phenol (MBPs) and maltose-tris(hydroxymethyl)phenol (MTPs). The evaluation of these detergents with three transporters and two G-protein coupled receptors allowed us to identify a couple of new detergents (MBP-C9 and MTP-C12) that consistently conferred enhanced stability to all tested proteins compared to a gold standard detergent (DDM). Furthermore, the data analysis based on the detergent structures provides key detergent features responsible for membrane protein stabilization that together will facilitate the future design of novel detergents.
U2 - 10.1021/acschembio.1c00578
DO - 10.1021/acschembio.1c00578
M3 - Journal article
C2 - 34445864
AN - SCOPUS:85114611689
VL - 16
SP - 1779
EP - 1790
JO - A C S Chemical Biology
JF - A C S Chemical Biology
SN - 1554-8929
IS - 9
ER -
ID: 279888599