Amphiphilic compounds
View Patent ↗Bringing membrane proteins into aqueous solution generally requires the use of detergents or other amphiphilic agents. The invention provides a new class of amphiphiles, each of which includes a multi-fused ring system as a lipophilic group. These new amphiphiles confer enhanced stability to a range of membrane proteins in solution relative to conventional detergents, leading to improved structural and functional stability of membrane proteins, including integral membrane proteins. Accordingly, the invention provides new amphiphiles for biochemical manipulations and characterization of membrane proteins. These amphiphiles display favorable behavior with membrane proteins and can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins.
1. A compound of Formula I:
wherein
L is —(CH 2 ) n — where n is 1-12, or a direct bond;
X is NH, O, or a direct bond;
Y is O or absent;
Z is H, methyl, ethyl, propyl, or butyl;
R x is H, (C 1 -C 24 )alkyl, aryl, or aroyl; and
each Sac is independently an oxygen-linked monosaccharide, disaccharide, or trisaccharide.
2. The compound of claim 1 , wherein R x is methyl.
3. The compound of claim 1 , wherein each Sac is an oxygen-linked monosaccharide.
4. The compound of claim 1 , wherein each Sac is an oxygen-linked disaccharide.
5. The compound of claim 1 , wherein each Sac is an oxygen-linked trisaccharide.
6. The compound of claim 1 , wherein X is NH, Y is O, Z is H, and L is a direct bond.
7. The compound of claim 1 , wherein L is —CH 2 —, X is O, Y is absent, and Z is Me.
8. The compound of claim 1 , wherein L is a direct bond, X is a direct bond, Y is absent, and Z is H.
9. The compound of claim 1 , wherein the compound is a compound of Formula II, III, or IV:
wherein DiSac is an oxygen-linked disaccharide.
10. The compound of claim 9 , wherein the compound is:
11. The compound of claim 1 , wherein the critical micelle concentration (CMC) of the compound in water is about 5 nM to about 100 nM.
12. The compound of claim 1 , wherein a plurality of the compounds form a micelle in water comprising about 5 to about 35 molecules of the compound.
13. A composition comprising a compound of claim 1 and an isolated membrane protein.
14. A micelle comprising a compound of claim 1 .
15. The micelle of claim 14 , further comprising a polypeptide or a protein.
16. A method of solubilizing or stabilizing a membrane protein comprising contacting a membrane protein with an effective amount of a compound as described by claim 1 , in an aqueous solution, and optionally heating the protein and the compound, thereby forming a solubilized or stabilized aggregation or micelle.
17. The method of claim 16 , comprising heating the protein and the compound, thereby forming a micelle.
18. A method of extracting a protein from a lipid bilayer comprising contacting the lipid bilayer with an effective amount of a compound of claim 1 in an aqueous solution to form a mixture, optionally in the presence of a buffer, thereby forming an aggregation of the compound and the membrane protein extracted from the lipid bilayer, and separating the aggregation from the mixture.