Cationic poly (amino acids) and uses thereof

1. A cationic poly(amino acid) of formula (1):

wherein:

R 1 is a hydroxyl group, an unsubstituted or substituted linear or branched alkyloxy group having 1 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkenyloxy group having 2 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkynyloxy group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkyl-substituted imino group having 1 to 12 carbon atoms;

R 2 is a hydrogen atom, an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkylcarbonyl group having 1 to 24 carbon atoms;

R 3a and R 3b are each independently a methylene group or an ethylene group;

R 4a and R 4b are each independently selected from the group consisting of:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2   (i);

—NH—(CH 2 ) p2 —N[—(CH 2 ) q2 —NH 2 ] 2   (ii);

—NH—(CH 2 ) p3 —N{[—(CH 2 ) q3 —NH 2 ][—(CH 2 ) q4 —NH] r2 H}  (iii); and

—NH—(CH 2 ) p4 —N{—(CH 2 ) q5 —N[—(CH 2 ) q6 —NH 2 ] 2 } 2   (iv),

wherein:

p1 to p4, q1 to q6, and r1 and r2 are each independently an integer of 1 to 5;

in 5 to 40% of all of the R 4a and R 4b groups, one hydrogen atom of at least one amino group is substituted with (i) an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms, or (ii) a steroloxycarbonyl group;

n is an integer of 30 to 5,000; and

y is an integer of 0 to 5,000,

provided that, when R 3a and R 3b are each a methylene group, y is less than n,

when n is less than y, n−y is set equal to zero, and

when n does not equal y and when y does not equal zero, the units having a number of repetitions n−y and the units having a number of repetitions y may be arranged in any order.

2. The poly(amino acid) of claim 1 , wherein R 3a and R 3b are each a methylene group in formula (1).

3. The poly(amino acid) of claim 2 , wherein:

R 4a and R 4b are each independently the group:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2   (i);

wherein:

p1 and q1 are each independently 2 or 3; and r1 is an integer of 1 to 3; and

in 10 to 30% of all of the R 4a and R 4b groups, one hydrogen atom of at least one amino group is substituted with an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms.

4. The poly(amino acid) of claim 3 , wherein n is 60 to 150.

5. A polyion complex, comprising:

the poly(amino acid) of claim 4 , wherein the acyl group is a stearoyl group; and

siRNA having a length of 18-30 bases bound to the poly(amino acid).

6. The poly(amino acid) of claim 1 , wherein R 3a is an ethylene group and y is 0 in formula (1).

7. The poly(amino acid) of claim 6 , wherein:

R 4a is the group:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2   (i);

wherein:

p1 and q1 are each independently 2 or 3; and r1 is an integer of 1 to 3; and

in 10 to 30% of all of the R 4a groups, one hydrogen atom of at least one amino group is substituted with an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms.

8. The poly(amino acid) of claim 1 , wherein:

R 4a and R 4b are each independently a the group:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 ] r1 NH 2   (i)

wherein:

p1 and q1 are each independently 2 or 3; and r1 is an integer of 1 to 3; and

in 10 to 30% of all of the R 4a and R 4b groups, one hydrogen atom of at least one amino group is substituted with an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms.

9. A polyion complex, comprising:

the poly(amino acid) of claim 1 ; and

a nucleic acid.

10. The complex of claim 9 , wherein the nucleic acid is selected from the group consisting of plasmid DNA, siRNA, micro RNA, an antisense nucleic acid, a decoy nucleic acid, an aptamer, and a ribozyme.

11. The poly(amino acid) of claim 1 , wherein R 4a and R 4b are the same group.

12. The poly(amino acid) of claim 1 , wherein p1 to p4 and q1 to q6 are each independently 2 or 3.

13. The poly(amino acid) of claim 1 , wherein p1 to p4 and q1 to q6 are each 2.

14. The poly(amino acid) of claim 1 , wherein r1 and r2 are each independently an integer of 1 to 3.

15. The poly(amino acid) of claim 1 , wherein R 1 is a hydroxyl group.

16. The poly(amino acid) of claim 1 , wherein R 1 is an unsubstituted or substituted linear or branched alkyloxy group having 1 to 12 carbon atoms.

17. The poly(amino acid) of claim 1 , wherein R 1 is an unsubstituted or substituted linear or branched alkenyloxy group having 2 to 12 carbon atoms.

18. The poly(amino acid) of claim 1 , wherein R 1 is an unsubstituted or substituted linear or branched alkynyloxy group having 1 to 12 carbon atoms.

19. The poly(amino acid) of claim 1 , wherein R 1 is an unsubstituted or substituted linear or branched alkyl-substituted imino group having 1 to 12 carbon atoms.

20. A block copolymer of formula (2):

wherein:

R 2 is a hydrogen atom, an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkylcarbonyl group having 1 to 24 carbon atoms;

R 3a and R 3b are each independently a methylene group or an ethylene group;

R 4a and R 4b are each independently selected from the group consisting of:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2   (i);

—NH—(CH 2 ) p2 —N[—(CH 2 ) q2 —NH 2 ] 2   (ii);

—NH—(CH 2 ) p3 —N{[—(CH 2 ) q3 —NH 2 ][—(CH 2 ) q4 —NH] r2 H}  (iii); and

—NH—(CH 2 ) p4 —N{—(CH 2 ) q5 —N[—(CH 2 ) q6 —NH 2 ] 2 } 2   (iv),

wherein:

p1 to p4, q1 to q6, and r1 and r2 are each independently an integer of 1 to 5;

in 5 to 40% of all of the R 4a and R 4b groups, one hydrogen atom of at least one amino group is substituted with (i) an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms, or (ii) a steroloxycarbonyl group;

n is an integer of 30 to 5,000; and

y is an integer of 0 to 5,000,

provided that, when R 3a and R 3b each represent a methylene group, y is less than n,

when n is less than y, n−y is set equal to zero, and

when n does not equal y and when y does not equal zero, the units having a number of repetitions n−y and the units having a number of repetitions y may be arranged in any order;

L 1 is —S—S— or a valence bond;

L 2 is —NH—, —O—, —O(CH 2 ) p1 —NH—, or -L 2a -(CH 2 ) q1 -L 2b -, wherein: p1 and q1 are each independently an integer of 1 to 5; L 2a is OCO, OCONH, NHCO, NHCOO, NHCONH, CONH, or COO; and L 2b is NH or O;

R 5 is a hydrogen atom or an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms; and

m is an integer of 30 to 20,000.

21. A polyion complex, comprising:

the block copolymer of claim 20 ; and

a nucleic acid.

22. The complex of claim 21 , wherein the nucleic acid is selected from the group consisting of plasmid DNA, siRNA, micro RNA, an antisense nucleic acid, a decoy nucleic acid, an aptamer, and a ribozyme.

23. The block copolymer of claim 20 , wherein:

R 3a and R 3b are each independently represent a methylene group,

R 4a and R 4b are each independently the group:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2   (i);

wherein:

p1 and q1 are each independently 2 or 3;

r1 is an integer of 1 to 3;

n is 60 to 150 and

in 10 to 30% of all of the R 4a and R 4b groups, one hydrogen atom of at least one amino group is substituted with an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms.

24. A polyion complex, comprising:

the block copolymer of claim 23 , wherein the acyl group is a stearoyl group; and

siRNA having a length of 18-30 bases bound to the poly(amino acid).

25. A composition of matter selected from the group consisting of the following formula (1) and formula (2):

wherein:

R 1 is a hydroxyl group, an unsubstituted or substituted linear or branched alkyloxy group having 1 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkenyloxy group having 2 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkynyloxy group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkyl-substituted imino group having 1 to 12 carbon atoms;

R 2 is a hydrogen atom, an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkylcarbonyl group having 1 to 24 carbon atoms;

R 3a and R 3b are each independently a methylene group or an ethylene group;

R 4a and R 4b are each independently selected from the group consisting of:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2   (i);

—NH—(CH 2 ) p2 —N[—(CH 2 ) q2 —NH 2 ] 2   (ii);

—NH—(CH 2 ) p3 —N{[—(CH 2 ) q3 —NH 2 ][—(CH 2 ) q4 —NH] r2 H}  (iii); and

—NH—(CH 2 ) p4 —N{—(CH 2 ) q5 —N[—(CH 2 ) q6 —NH 2 ] 2 } 2   (iv),

wherein:

p1 to p4, q1 to q6, and r1 and r2 are each independently an integer of 1 to 5;

in 5 to 40% of all of the R 4a and R 4b groups, one hydrogen atom of at least one amino group in which a hydrogen atom is substituted with (i) an acyl group having a saturated or unsaturated linear or branched aliphatic hydrocarbon residue having 6 to 27 carbon atoms, or (ii) a steroloxycarbonyl group;

n is an integer of 30 to 5,000; and

y is an integer of 0 to 5,000,

provided that, when R 3a and R 3b are each a methylene group, y is less than n,

when n is less than y, n−y is set equal to zero, and

when n does not equal y and when y does not equal zero, the units having a number of repetitions n−y and the units having a number of repetitions y may be arranged in any order;

L 1 is —S—S— or a valence bond;

L 2 is —NH—, —O—, —O(CH 2 ) p1 —NH—, or -L 2a -(CH 2 ) q1 -L 2b -, wherein: p1 and q1 are each independently represent an integer of 1 to 5; L 2a is OCO, OCONH, NHCO, NHCOO, NHCONH, CONH, or COO; and L 2b is NH or O;

R 5 is a hydrogen atom or an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms; and

m is an integer of 30 to 20,000.