Amphiphiles for protein solubilization and stabilization

1. An amphiphilic compound of Formula I:

wherein

each R is independently C 1 -C 16 straight or branched alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, or C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups; or

the two R groups together with the carbon to which they are attached form a C 3 -C 8 cycloalkyl, a C 3 -C 8 cycloalkenyl, or an adamantyl ring;

R 1 is C 1 -C 16 straight or branched alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, halophenyl, p-tolyl, adamantyl or C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, halophenyl, p-tolyl, adamantyl substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups; or

R, R, and R 1 together with the carbon to which they are attached form an adamantyl ring, optionally substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups;

X is CH 2 or a direct bond;

R 2 is H, an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two or more glycosyl residues;

R 3 is an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two or more glycosyl residues, or a C 1 -C 4 alkyl-(N,N-dimethyl)N-oxide; and

R 4 is an O-linked C 6 glycosyl residue, an O-linked oligosaccharide comprising two or more glycosyl residues, or a C 1 -C 4 alkyl-(N,N-dimethyl)N-oxide.

2. The amphiphilic compound of claim 1 wherein each R is independently ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, adamantyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; and

R 1 is C 1 -C 16 n-alkyl, isobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, halophenyl, p-tolyl, p-isopropyl phenyl, p-t-butylphenyl, or p-biphenyl.

3. The amphiphilic compound of claim 2 wherein each R is n-butyl and R 1 is phenyl; each R is n-butyl and R 1 is cyclohexyl; each R is n-butyl and R 1 is isobutyl; each R is n-butyl and R 1 is p-iodophenyl; each R is ethyl and R 1 is isobutyl; each R is n-butyl and R 1 is p-tolyl; each R is n-butyl and R 1 is p-isopropyl phenyl; each R is n-butyl and R 1 is p-t-butyl phenyl; each R is n-pentyl and R 1 is phenyl; or each R is n-hexyl and R 1 is phenyl.

4. The amphiphilic compound of claim 1 wherein the compound of Formula I is a compound of Formula II:

wherein R 5 is H or a C 6 glycosyl residue.

5. The amphiphilic compound of claim 1 wherein X is a direct bond and R 2 is H.

6. The amphiphilic compound of claim 5 wherein the compound of Formula I is a compound of Formula III:

wherein R 5 is H or a C 6 glycosyl residue.

7. The amphiphilic compound of claim 1 wherein one or both of R 3 and R 4 are O-linked glucose, mannose, galactose, maltose, or sucrose residues.

8. An amphiphilic compound of Formula IV:

wherein

one R is H and the other R is C 1 -C 16 straight or branched alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, or C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups; or

the two R groups together with the carbon to which they are attached form an adamantyl ring;

R 1 is C 1 -C 16 straight or branched alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, halophenyl, p-tolyl, adamantyl or C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, halophenyl, p-tolyl, adamantyl substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups; or

R, R, and R 1 together with the carbon to which they are attached form an adamantyl ring, optionally substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups;

each X is independently CH 2 or a direct bond;

R 2 is H, an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two glycosyl residues;

R 3 is H, an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two glycosyl residues; and

R 4 is an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two glycosyl residues.

9. The amphiphilic compound of claim 8 wherein each R is independently ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, adamantyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; and

R 1 is C 1 -C 16 n-alkyl, isobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, halophenyl, p-tolyl, p-isopropyl phenyl, p-t-butylphenyl, or p-biphenyl.

10. An amphiphilic compound wherein the compound is:

11. The amphiphilic compound of claim 8 wherein the two R groups together with the carbon to which they are attached form an adamantyl ring; R 1 is a C 1 -C 16 straight or branched alkyl; —X—R 2 is direct bond-H; —X—R 3 is direct bond-H or —CH 2 —O-linked C 6 glycosyl residue or O-linked oligosaccharide comprising two glycosyl residues.

12. The amphiphilic compound of claim 11 wherein the compound is:

13. The amphiphilic compound of claim 8 wherein the compound of Formula IV is a compound of Formula V:

wherein R 5 is H or a C 6 glycosyl residue; and

each R 6 is independently H or C 1 -C 6 alkyl.

14. The amphiphilic compound of claim 13 wherein the compound is:

15. An amphiphilic compound of Formula VI:

wherein R is H, C 1 -C 16 straight or branched alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl, or C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, phenyl, biphenyl substituted with one, two, or three C 1 -C 6 straight or branched alkyl groups;

each X is independently CH 2 or a direct bond;

R 2 is H, an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two or more glycosyl residues;

R 3 is H, an O-linked C 6 glycosyl residue, or an O-linked oligosaccharide comprising two or more glycosyl residues, or a C 1 -C 4 alkyl-(N,N-dimethyl)N-oxide; and

R 4 is an O-linked C 6 glycosyl residue, an O-linked oligosaccharide comprising two or more glycosyl residues, or a C 1 -C 4 alkyl-(N,N-dimethyl)N-oxide.

16. The amphiphilic compound of claim 15 wherein R is a C 3 -C 10 branched alkyl.

17. The amphiphilic compound of claim 16 wherein —X—R 2 is direct bond-H; —X—R 3 is direct bond-H or —CH 2 —O-linked C 6 glycosyl residue or O-linked oligosaccharide comprising two or more glycosyl residues; and R 4 is O-linked C 6 glycosyl residue or O-linked oligosaccharide comprising two or more glycosyl residues, or a C 1 -C 4 alkyl-(N,N-dimethyl)N-oxide.

18. The amphiphilic compound of claim 17 wherein the compound is:

19. A method for solubilizing or stabilizing a membrane protein comprising contacting a protein in an aqueous environment with an effective amount of a compound of claim 1 , and

optionally heating the protein and the compound, to provide the solubilized protein encapsulated in micelles of the compound.

20. A method for solubilizing or stabilizing a membrane protein comprising contacting a protein in an aqueous environment with an effective amount of a compound of claim 8 , and

optionally heating the protein and the compound, to provide the solubilized protein encapsulated in micelles of the compound.

21. A method for solubilizing or stabilizing a membrane protein comprising contacting a protein in an aqueous environment with an effective amount of a compound of claim 15 , and

optionally heating the protein and the compound, to provide the solubilized protein encapsulated in micelles of the compound.

22. The amphiphilic compound of claim 1 wherein the compound is: