A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study

TY - JOUR

T1 - A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study

AU - Sadaf, Aiman

AU - Mortensen, Jonas S

AU - Capaldi, Stefano

AU - Tikhonova, Elena

AU - Hariharan, Parameswaran

AU - de Castro Ribeiro, Orquidea

AU - Loland, Claus J

AU - Guan, Lan

AU - Byrne, Bernadette

AU - Chae, Pil Seok

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Membrane proteins are amphipathic bio-macromolecules incompatible with the polar environments of aqueous media. Conventional detergents encapsulate the hydrophobic surfaces of membrane proteins allowing them to exist in aqueous solution. Membrane proteins stabilized by detergent micelles are used for structural and functional analysis. Despite the availability of a large number of detergents, only a few agents are sufficiently effective at maintaining the integrity of membrane proteins to allow successful crystallization. In the present study, we describe a novel class of synthetic amphiphiles with a branched tail group and a triglucoside head group. These head and tail groups were connected via an amide or ether linkage by using a tris(hydroxylmethyl)aminomethane (TRIS) or neopentyl glycol (NPG) linker to produce TRIS-derived triglucosides (TDTs) and NPG-derived triglucosides (NDTs), respectively. Members of this class conferred enhanced stability on target membrane proteins compared to conventional detergents. Because of straightforward synthesis of the novel agents and their favourable effects on a range of membrane proteins, these agents should be of wide applicability to membrane protein science.

AB - Membrane proteins are amphipathic bio-macromolecules incompatible with the polar environments of aqueous media. Conventional detergents encapsulate the hydrophobic surfaces of membrane proteins allowing them to exist in aqueous solution. Membrane proteins stabilized by detergent micelles are used for structural and functional analysis. Despite the availability of a large number of detergents, only a few agents are sufficiently effective at maintaining the integrity of membrane proteins to allow successful crystallization. In the present study, we describe a novel class of synthetic amphiphiles with a branched tail group and a triglucoside head group. These head and tail groups were connected via an amide or ether linkage by using a tris(hydroxylmethyl)aminomethane (TRIS) or neopentyl glycol (NPG) linker to produce TRIS-derived triglucosides (TDTs) and NPG-derived triglucosides (NDTs), respectively. Members of this class conferred enhanced stability on target membrane proteins compared to conventional detergents. Because of straightforward synthesis of the novel agents and their favourable effects on a range of membrane proteins, these agents should be of wide applicability to membrane protein science.

U2 - 10.1039/C5SC02900G

DO - 10.1039/C5SC02900G

M3 - Journal article

C2 - 27110345

SN - 2041-6520

VL - 7

SP - 1933

EP - 1939

JO - Chemical Science

JF - Chemical Science

IS - 3

ER -