Amino acid lipids and uses thereof
View Patent ↗This disclosure provides a range of amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.
1. A compound comprising the structure shown in Formula I:
R 3 —(C═O)—Xaa-Z—R 4 Formula I
wherein
Xaa is histidine or a side chain N-methylated histidine;
R 3 is independently a substituted or unsubstituted C(12-22)alkyl or C(12-22)alkenyl;
R 4 is independently a substituted or unsubstituted C(12-22)alkyl or C(12-22)alkenyl;
Z is NH;
wherein at least one of R 3 and R 4 is alkenyl;
and salts thereof.
2. The compound of claim 1 , wherein R 3 and R 4 are C(12-22)alkenyl and are the same or different.
3. The compound of claim 1 , wherein R 3 is C(12-22)alkyl and R 4 is C(12-22)alkenyl.
4. The compound of claim 1 , wherein R 4 is C(12-22)alkyl and R 3 is C(12-22)alkenyl.
5. A compound comprising the structure shown in Formula I:
R 3 —(C═O)—Xaa-Z—R 4 Formula I
wherein
Xaa is histidine or a side chain N-methylated histidine;
R 3 is independently a substituted or unsubstituted C(12-22)alkyl or C(12-22)alkenyl;
R 4 is independently a substituted or unsubstituted C(12-22)alkyl or C(12-22)alkenyl;
Z is NH;
wherein a peptide is attached to the side chain of Xaa;
and salts thereof.
6. The compound of claim 1 , wherein the compound is attached to an oligomeric or polymeric framework.
7. The compound of claim 1 , wherein the compound is attached to a pharmaceutical drug compound.
8. The compound of claim 1 , and selected from (C18oleic)-His-NH—(C12alkyl), (C18oleic)-His-NH—(C16alkyl), and (C18oleic)-His-NH—(C18alkyl).
9. The compound N-(3-(1-methyl-1H-imidazol-4-yl)-1-oxo-1-(hexadecylamino)propan-2-yl)octadec-9-enamide which is (C18oleic)-(1-CH 3 -His)-NH—(C16alkyl).
10. A composition comprising one or more compounds according to claim 1 and one or more therapeutic nucleic acids.
11. The composition of claim 10 , wherein the therapeutic nucleic acid is a gene silencing agent.
12. The composition of claim 10 , wherein the therapeutic nucleic acid is a RNAi-inducing agent.
13. The composition of claim 10 , wherein the therapeutic nucleic acid is a double-stranded RNA.
14. The composition of claim 10 , wherein the therapeutic nucleic acid is an mdRNA.
15. The composition of claim 10 , wherein the therapeutic nucleic acid contains a modified nucleoside.
16. The composition of claim 10 , further comprising one or more non-cationic lipids or sterols.
17. The composition of claim 10 , further comprising cholesteryl hemisuccinate.
18. The composition of claim 10 , further comprising one or more cationic lipids.
19. The composition of claim 10 , further comprising one or more pegylated lipids or pegylated sterols.
20. The composition of claim 10 , wherein the composition contains liposomes.
21. The composition of claim 10 , wherein the composition is an emulsion.
22. The composition of claim 10 , wherein the composition is a micellar dispersion.
23. A pharmaceutical composition comprising one or more compounds according to claim 1 and one or more drug agents or biologically active agents.
24. A method for delivering a therapeutic nucleic acid to a cell comprising preparing a composition according to claim 10 and treating a cell with the composition.
25. A method for inhibiting expression of a gene in a cell comprising preparing a composition according to claim 10 and treating a cell with the composition.
26. A method for inhibiting expression of a gene in a mammal comprising preparing a composition according to claim 10 and administering the composition to the mammal.
27. A method for treating a disease in a human, the disease being selected from rheumatoid arthritis, liver disease, encephalitis, bone fracture, heart disease, viral disease, hepatitis, influenza, sepsis, and cancer, the method comprising preparing a composition according to claim 10 and administering the composition to the human.