Biodegradable compound, lipid particle, composition containing lipid particle, and kit
The compound according to the present embodiment is represented by the following formula (1): Q-L-CHR 2 (1) (wherein, Q is a non-cationic aliphatic group that does not contain nitrogen but contains oxy; L is a single bond or an aliphatic group containing no nitrogen; Rs are C 12 -C 24 aliphatic group, the same or different; and at least one R contains, in the main chain or side chain thereof, a linking group L R selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, —C(═O)—S—, —C(═O)—NH—, and —NH—C(═O)—).
1. A compound represented by the following formula (1):
Q-L-CHR 2 (1)
wherein,
Q is a non-cationic aliphatic group which is represented by the following formula (1B-1):
Q 0 -[(CH 2 ) b1 —O-] b2 - (1B-1)
wherein
Q 0 is hydrogen, halogen, alkyl, or alkenyl;
b1 is a number from 0 to 3;
b2 is a number from 1 to 3; and
the total number of carbon atoms contained in the formula (1B-1) is 6 or less;
L is an aliphatic group which is represented by the following formula (1A):
-L A a -L 0 -L A a - (1A)
wherein
L A is alkylene or cycloalkylene that is optionally substituted independently with oxygen;
L 0 is an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, and —C(═O)—S—, and a is independently a number from 0 to 6);
Rs are C 12 -C 24 aliphatic groups, the same or different; and at least one R contains, in the main chain or side chain thereof, a linking group L R selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, —C(═O)—S—, —C(═O)—NH—, and —NH—C(═O)—.
2. The compound according to claim 1 , wherein the L contains an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —C(═S)—O—, —O—C(═S)—, —O—C(═S)—O—, —S—C(═O)—, and —C(═O) S—.
3. The compound according to claim 1 , wherein the Q is represented by the following formula (1B-2):
Q 1 -L B - (1B-2)
wherein,
Q 1 is a cyclo ether; and
L B is alkylene.
4. The compound according to claim 1 , wherein the at least one R is represented by the following formula (1C):
-L C1 -C(═O)—O-L C2 (1C)
wherein,
L C1 is alkylene; and
L C2 is alkenyl.
5. The compound according to claim 4 , wherein the L C1 and the L C2 are represented by the following formulae (1C-1) and (1C-2) respectively:
—(CH 2 ) c1 -(1C-1)
—CH 2 —CH═CH—(CH 2 ) c2 —H(1C-2)
wherein
c1 is a number from 1 to 10; and
c2 is a number from 1 to 10.
6. The compound according to claim 5 , wherein the c1 is a number from 4 to 8.
7. The compound according to claim 1 , wherein the longest molecular chain contained in the R has 8 or more atoms.
8. The compound according to claim 1 , wherein is said compound is a compound presented by one of the following formulae (1-01), (1-02), (1-05) to (1-12), and (1-14) to (1-20)
9. A lipid particle comprising the compound according to claim 1 .
10. The lipid particle according to claim 9 , further comprising a membrane-forming lipid and an aggregation-reducing lipid.
11. The lipid particle according to claim 10 , wherein the membrane-forming lipid is selected from the group consisting of
1,2-dioleoyl-sn-glycero-3-phosphoethanol amine (DOPE),
1,2-stearoyl-sn-glycero-3-phosphoethanol amine (DSPE),
1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC),
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC),
1,2-di-O-octadecyl-3-trimethylammonium propane (DOTMA),
1,2-dioleoyl-3-dimethylammonium propane (DODAP),
1,2-dimyristoyl-3-di methylammonium propane (14:0 DAP),
1,2-dipalmitoyl-3-dimethylammonium propane (16:0 DAP),
1,2-distearoyl-3-dimethylammonium propane (18:0 DAP),
N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propane (DOBAQ),
1,2-dioleoyl-3-trimethylammonium propane (DOTAP),
1,2-dioleoyl-sn-glycero-3-phosphochlorine (DOPC),
1,2-dilinoleoyl-sn-glycero-3-phosphochlorine (DLPC),
1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), cholesterol, and the like; and
wherein the aggregation-reducing lipid is a polyethylene glycol (PEG)-modified lipid.
12. The lipid particle according to claim 9 , further comprising an active agent.
13. The lipid particle according to claim 12 , wherein the active agent is a nucleic acid selected from the group consisting of plasmids, oligonucleotides, polynucleotides, siRNAs, micro RNAs, DNAs, aptamers, and ribozymes.
14. The lipid particle according to claim 13 , further comprising a compound that binds to a nucleic acid.
15. The lipid particle according to claim 14 , wherein the compound that binds to a nucleic acid is a basic protein or a basic peptide.
16. The lipid particle according to claim 14 , wherein the compound that binds to a nucleic acid is a protamine or a histone.
17. The lipid particle according to claim 14 , further comprising a compound that regulates the expression of a nucleic acid in a cell.
18. A composition comprising the lipid particle according to claim 9 and a carrier.
19. A kit comprising the lipid particle according to claim 9 and a composition containing an incorporation agent for incorporating the lipid particle into a cell.
20. A compound represented by the following formula (1):
Q-L-CHR 2 (1)
wherein,
Q is a non-cationic aliphatic group that does not contain nitrogen but contains oxy;
L is a single bond or an aliphatic group containing no nitrogen;
Rs are C 12 -C 24 aliphatic groups, the same or different; and at least one R is represented by the following formula (1C):
—(CH 2 ) c1 —C(═O)—O—CH 2 —CH═CH—(CH 2 ) c2 —H (1C)
wherein,
c1 is a number from 1 to 10; and
c2 is a number from 1 to 10.
21. The compound according to claim 20 , wherein the L contains an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —C(═S)—O—, —O—C(═S)—, —O—C(═S)—O—, —S—C(═O)—, and —C(═O) S—.
22. The compound according to claim 20 , wherein the L is represented by the following formula (1A):
-L A a -L 0 -L A a - (1A)
wherein
L A is alkylene or cycloalkylene that is optionally substituted independently with oxygen;
L 0 is an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, and —C(═O)—S—, and a is independently a number from 0 to 6.
23. The compound according to claim 22 , wherein the Q is represented by the following formula (1B-1):
Q 0 -[(CH 2 ) b1 —O—] b2 - (1B-1)
wherein
Q 0 is hydrogen, halogen, alkyl, or alkenyl;
b1 is a number from 0 to 3;
b2 is a number from 1 to 3; and
the total number of carbon atoms contained in the formula (1B-1) is 6 or less.
24. The compound according to claim 22 , wherein the Q is represented by the following formula (1B-2):
Q 1 -L B - (1B-2)
wherein,
Q 1 is a cyclo ether; and
L B is alkylene.
25. The compound according to claim 20 , wherein the c1 is a number from 4 to 8.
26. The compound according to claim 20 , wherein the longest molecular chain contained in the R has 8 or more atoms.
27. The compound according to claim 20 , wherein said compound is a compound presented by one of the following formulae (1-01) to (1-12) and (1-14) to (1-20)
28. A lipid particle comprising the compound according to claim 20 .
29. The lipid particle according to claim 28 , further comprising a membrane-forming lipid and an aggregation-reducing lipid.
30. The lipid particle according to claim 29 , wherein the membrane-forming lipid is selected from the group consisting of
1,2-dioleoyl-sn-glycero-3-phosphoethanol amine (DOPE),
1,2-stearoyl-sn-glycero-3-phosphoethanol amine (DSPE),
1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC),
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC),
1,2-di-O-octadecyl-3-trimethylammonium propane (DOTMA),
1,2-dioleoyl-3-dimethylammonium propane (DODAP),
1,2-dimyristoyl-3-di methylammonium propane (14:0 DAP),
1,2-dipalmitoyl-3-dimethylammonium propane (16:0 DAP),
1,2-distearoyl-3-dimethylammonium propane (18:0 DAP),
N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propane (DOBAQ),
1,2-dioleoyl-3-trimethylammonium propane (DOTAP),
1,2-dioleoyl-sn-glycero-3-phosphochlorine (DOPC),
1,2-dilinoleoyl-sn-glycero-3-phosphochlorine (DLPC),
1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), cholesterol, and the like; and
wherein the aggregation-reducing lipid is a polyethylene glycol (PEG)-modified lipid.
31. The lipid particle according to claim 28 , further comprising an active agent.
32. The lipid particle according to claim 31 , wherein the active agent is a nucleic acid selected from the group consisting of plasmids, oligonucleotides, polynucleotides, siRNAs, micro RNAs, DNAs, aptamers, and ribozymes.
33. The lipid particle according to claim 32 , further comprising a compound that binds to a nucleic acid.
34. The lipid particle according to claim 33 , wherein the compound that binds to a nucleic acid is a basic protein or a basic peptide.
35. The lipid particle according to claim 33 , wherein the compound that binds to a nucleic acid is a protamine or a histone.
36. The lipid particle according to claim 33 , further comprising a compound that regulates the expression of a nucleic acid in a cell.
37. A lipid particle comprising the compound which is represented by the following formula (1):
Q-L-CHR 2 (1)
wherein,
Q is a non-cationic aliphatic group that does not contain nitrogen but contains oxy;
L is a single bond or an aliphatic group containing no nitrogen;
Rs are C 12 -C 24 aliphatic groups, the same or different; and at least one R contains, in the main chain or side chain thereof, a linking group L R selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, —C(═O)—S—, —C(═O)—NH—, and —NH—C(═O)—,
a membrane-forming lipid, and
an aggregation-reducing lipid.
38. The lipid particle according to claim 37 , wherein the membrane-forming lipid is selected from the group consisting of
1,2-dioleoyl-sn-glycero-3-phosphoethanol amine (DOPE),
1,2-stearoyl-sn-glycero-3-phosphoethanol amine (DSPE),
1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC),
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC),
1,2-di-O-octadecyl-3-trimethylammonium propane (DOTMA),
1,2-dioleoyl-3-dimethylammonium propane (DODAP),
1,2-dimyristoyl-3-di methylammonium propane (14:0 DAP),
1,2-dipalmitoyl-3-dimethylammonium propane (16:0 DAP),
1,2-distearoyl-3-dimethylammonium propane (18:0 DAP),
N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propane (DOBAQ),
1,2-dioleoyl-3-trimethylammonium propane (DOTAP),
1,2-dioleoyl-sn-glycero-3-phosphochlorine (DOPC),
1,2-dilinoleoyl-sn-glycero-3-phosphochlorine (DLPC),
1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), cholesterol, and the like; and
wherein the aggregation-reducing lipid is a polyethylene glycol (PEG)-modified lipid.
39. The lipid particle according to claim 37 , further comprising an active agent.
40. The lipid particle according to claim 39 , wherein the active agent is a nucleic acid selected from the group consisting of plasmids, oligonucleotides, polynucleotides, siRNAs, micro RNAs, DNAs, aptamers, and ribozymes.
41. The lipid particle according to claim 40 , further comprising a compound that binds to a nucleic acid.
42. The lipid particle according to claim 41 , wherein the compound that binds to a nucleic acid is a basic protein or a basic peptide.
43. The lipid particle according to claim 41 , wherein the compound that binds to a nucleic acid is a protamine or a histone.
44. The lipid particle according to claim 41 , further comprising a compound that regulates the expression of a nucleic acid in a cell.
45. A composition comprising the lipid particle according to claim 28 and a carrier.
46. A kit comprising the lipid particle according to claim 28 and a composition containing an incorporation agent for incorporating the lipid particle into a cell.
47. A composition comprising the lipid particle according to claim 37 and a carrier.
48. A kit comprising the lipid particle according to claim 37 and a composition containing an incorporation agent for incorporating the lipid particle into a cell.