Synthetic amphiphiles for membrane protein manipulation
View Patent ↗The invention provides amphiphilic compounds and methods for manipulating membrane proteins. Compounds of the invention, for example, the compounds of Formulas I-XIX, can be prepared from readily available starting materials. The amphiphilic compounds can manipulate membrane protein at relatively low concentrations compared to many known detergents. The compounds can be used to aid the isolation of membrane proteins, for example, to aid their solubilization and/or purification. The compounds can also be used to aid the functional and structural determination of membrane proteins, including their stabilization and crystallization.
1. A compound of Formula I:
wherein
R 1 =R 2 =(C 3 -C 20 )cycloalkyl(C 1 -C 20 )alkyl;
each X is independently —O—, —S—, —CH 2 —, —C(═O)NH—, or a direct bond;
P 1 is a disaccharide, —N(R 3 )-monosaccharide, —N(R 3 )-disaccharide, or —Y—(C 1 -C 6 )alkyl-Z;
P 2 is a disaccharide, —N(R 3 )-monosaccharide, —N(R 3 )-disaccharide, or —Y—(C 1 -C 6 )alkyl-Z;
each Y is independently —C(═O)NH—, —CH 2 —, or a direct bond;
each Z is independently —N + (O − )(Me) 2 , —OP(═O)(O − )—(C 1 -C 6 )alkyl-N((C 1 -C 3 )alkyl) 3 , —N + (Me) 2 -(C 1 -C 6 )alkyl-SO 3 − , or —N + (Me) 2 -(C 1 -C 6 )alkyl-CO 2 − ; and
each R 3 is independently hydrogen or (C 1 -C 6 )alkyl optionally substituted with a hydroxy group.
2. The compound of claim 1 , wherein P 1 =P 2 =disaccharide.
3. The compound of claim 2 , wherein X is a direct bond.
4. A compound of Formula I:
wherein
R 1 =R 2 =cyclohexyl(C 1 -C 20 )alkyl;
each X is independently —O—, —S—, —CH 2 —, —C(═O)NH—, or a direct bond;
P 1 is a monosaccharide, a disaccharide, —N(R 3 )-monosaccharide, —N(R 3 )-disaccharide, or —Y—(C 1 -C 6 )alkyl-Z;
P 2 is a monosaccharide, a disaccharide, —N(R 3 )-monosaccharide, —N(R 3 )-disaccharide, or —Y—(C 1 -C 6 )alkyl-Z;
each Y is independently —C(═O)NH—, —CH 2 —, or a direct bond;
each Z is independently —N + (O − )(Me) 2 , —OP(═O)(O − )—(C 1 -C 6 )alkyl-N((C 1 -C 3 )alkyl) 3 , —N + (Me) 2 -(C 1 -C 6 )alkyl-SO 3 − , or —N + (Me) 2 -(C 1 -C 6 )alkyl-CO 2 − ; and
each R 3 is independently hydrogen or (C 1 -C 6 )alkyl optionally substituted with a hydroxy group.
5. The compound of claim 4 , wherein P 1 =P 2 =disaccharide.
6. The compound of claim 5 , wherein the disaccharide is maltose or sucrose.
7. The compound of claim 5 , wherein the disaccharide comprises a pyranoside or a furanoside.
8. The compound of claim 5 , wherein the disaccharide is maltopyranoside.
9. The compound of claim 8 , wherein the disaccharide is β-D-maltopyranoside.
10. The compound:
11. The compound:
12. The compound: