Polyhydroxy diamine surfactants and their use in gene transfer
The use of carbohydrate-based surfactant compounds having the general formula (I): wherein Y 1 and Y 2 , which may be the same or different, are carbohydrate groups; R 1 and R 2 , which may be the same or different, are selected from: a) hydrogen; b) C (1-24) alkyl group; c) C (1-24) alkyl carboxy group; or d) a carbon chain of 2 to 24 carbon atoms having one or more carbon/carbon double bonds, and n is from 1 to 10; for facilitating the transfer of DNA or RNA polynucleotides, or analogs thereof, into a eukaryotic or prokaryotic cell in vivo or in vitro. New carbohydrate-based surfactant compounds are also disclosed.
1. A method of transferring a DNA or RNA polynucleotide into a eukaryotic cell in vivo or in vitro, the method comprising contacting the cell with a DNA or RNA polynucleotide and a compound of formula (I):
wherein Y 1 and Y 2 , which may be the same or different, are carbohydrate groups;
R 1 and R 2 , which may be the same or different, are selected from the group consisting of:
hydrogen,
C (1–24) alkyl group,
C (1-24) alkyl carboxy group, and
a carbon chain of 2 to 24 carbon atoms having one or more carbon/carbon double bonds;
and n is from 1 to 10;
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 wherein the carbohydrate groups Y 1 and Y 2 are sugars.
3. The method of claim 1 wherein R 1 and R 2 are alkyl groups of chain-length C (10-20) and n is between 2 and 8.
4. The method of claim 3 wherein R 1 and R 2 are alkyl groups of chain-length C (12-18) and n is 4 or 6.
5. The method of claim 1 wherein R 1 and R 2 are carbon chains of 2 to 24 carbon atoms having one or more carbon/carbon double bonds.
6. The method of claim 5 wherein the carbon chains have 18 carbon atoms.
7. The method of claim 1 wherein the compound is symmetrical, that is the groups R 1 and R 2 are the same, and Y 1 and Y 2 are the same.
8. The method of claim 1 wherein the polynucleotide is transferred into the cell in culture.
9. A compound of formula (I):
wherein Y1 and Y2, which may be the same or different, are carbohydrate groups; one of R1 and R2 is selected from the group consisting of hydrogen, a C (1-24) alkyl group, a C (1-24) alkylcarboxy group, and a carbon chain of 2 to 24 carbon atoms having one or more carbon/carbon double bonds; the other of R1 and R2 is selected from the group consisting of a C (1-24) alkyl group and a carbon chain of 2 to 24 carbon atoms having one or more carbon/carbon double bonds; and n is from 1 to 10; or a pharmaceutically acceptable salt thereof.
10. The compound of claim 9 wherein R 1 and R 2 are alkyl groups of chain-length C (10-20) and n is between 2 and 8.
11. The compound of claim 9 wherein R 1 and R 2 are each oleyl, C 12 -alkyl, C 14 -alkyl, C 16 -alkyl, or C 18 -alkyl; Y 1 and Y 2 are each glucitol; and n is 4 or 6.
12. The compound of claim 9 wherein the compound is a gemini compound where R 1 and R 2 are the same and Y 1 and Y 2 are the same.
13. The compound of claim 12 which has the formula (II):
wherein Glu is glucose in open chain form (glucitol).
14. The compound of claim 9 wherein one of R 1 and R 2 is an alkyl group of chain-length C (1-24) , and the other of R 1 and R 2 is a C (1-24) alkyl carboxy group.
15. The compound of claim 9 wherein R 1 and R 2 are carbon chains of 2 to 24 carbon atoms having one or more carbon/carbon double bonds.
16. The compound of claim 15 wherein the carbon chain has 18 carbon atoms.