TY - JOUR

T1 - Resorcinarene-Based Facial Glycosides

T2 - Implication of Detergent Flexibility on Membrane-Protein Stability

AU - Hussain, Hazrat

AU - Du, Yang

AU - Tikhonova, Elena

AU - Mortensen, Jonas S.

AU - Ribeiro, Orquidea

AU - Santillan, Claudia

AU - Das, Manabendra

AU - Ehsan, Muhammad

AU - Loland, Claus J.

AU - Guan, Lan

AU - Kobilka, Brian K.

AU - Byrne, Bernadette

AU - Chae, Pil Seok

PY - 2017

Y1 - 2017

N2 - As a membrane-mimetic system, detergent micelles are popularly used to extract membrane proteins from lipid environments and to maintain their solubility and stability in an aqueous medium. However, many membrane proteins encapsulated in conventional detergents tend to undergo structural degradation during extraction and purification, thus necessitating the development of new agents with enhanced properties. In the current study, two classes of new amphiphiles are introduced, resorcinarene-based glucoside and maltoside amphiphiles (designated RGAs and RMAs, respectively), for which the alkyl chains are facially segregated from the carbohydrate head groups. Of these facial amphiphiles, two RGAs (RGA-C11 and RGA-C13) conferred markedly enhanced stability to four tested membrane proteins compared to a gold-standard conventional detergent. The relatively high water solubility and micellar stability of the RGAs compared to the RMAs, along with their generally favourable behaviours for membrane protein stabilisation described here, are likely to be, at least in part, a result of the high conformational flexibility of these glucosides. This study suggests that flexibility could be an important factor in determining the suitability of new detergents for membrane protein studies.

AB - As a membrane-mimetic system, detergent micelles are popularly used to extract membrane proteins from lipid environments and to maintain their solubility and stability in an aqueous medium. However, many membrane proteins encapsulated in conventional detergents tend to undergo structural degradation during extraction and purification, thus necessitating the development of new agents with enhanced properties. In the current study, two classes of new amphiphiles are introduced, resorcinarene-based glucoside and maltoside amphiphiles (designated RGAs and RMAs, respectively), for which the alkyl chains are facially segregated from the carbohydrate head groups. Of these facial amphiphiles, two RGAs (RGA-C11 and RGA-C13) conferred markedly enhanced stability to four tested membrane proteins compared to a gold-standard conventional detergent. The relatively high water solubility and micellar stability of the RGAs compared to the RMAs, along with their generally favourable behaviours for membrane protein stabilisation described here, are likely to be, at least in part, a result of the high conformational flexibility of these glucosides. This study suggests that flexibility could be an important factor in determining the suitability of new detergents for membrane protein studies.

KW - facial amphiphiles

KW - membrane proteins

KW - molecular design

KW - protein stability

KW - resorcinarene glycosides

U2 - 10.1002/chem.201605016

DO - 10.1002/chem.201605016

M3 - Journal article

C2 - 28303608

AN - SCOPUS:85018625595

VL - 23

SP - 6724

EP - 6729

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 28

ER -