Arginine-based antibacterial polymers with UCST property
The present invention concerns a polymer comprising repetitive units having the following formula (I) wherein R 1 is H or Me; L is a linker; R 2 is the side chain of an α-amino acid being other than arginine; m is 0 or an integer comprised from 1 to 10; n is an integer comprised from 1 to 10; and X— is a counterion.
1. A polymer comprising repetitive units having the following formula (I):
wherein:
R 1 is H or Me;
L is a linker;
R 2 is the side chain of an α-amino acid being other than arginine;
m is 0 or an integer comprised from 1 to 10;
n is an integer comprised from 1 to 10; and
X − is a counterion.
2. The polymer of claim 1 , wherein L is a linker having the following formula (II):
-A 1 -A 2 -A 3 - (II)
wherein:
A 1 is a (C 1 -C 6 )alkylene group;
A 2 is a group obtained by alkyne-azide cycloaddition reaction; and
A 3 is a (C 1 -C 10 )alkylene group, optionally interrupted by one or several oxygen atoms.
3. The polymer of claim 2 , wherein A 2 is a triazole group.
4. The polymer of claim 1 , wherein L has the following formula:
5. The polymer of claim 1 , wherein m=0.
6. The polymer of claim 5 , further comprising repetitive units having the following formula (IV):
wherein:
p is an integer comprised from 1 to 10.
7. The polymer of claim 1 , having the following formula (V):
wherein:
R 1 , L, R 2 , X − , m, and n are as defined in claim 1 ;
R 3 represents an aliphatic or aromatic chain, optionally substituted by one or several functional groups and/or optionally interrupted by one or several oxygen atoms;
R 4 represents a group —S—C(═S)—Z, Z being the group controlling the reactivity of the C═S bond; and
q is comprised from 2 to 100.
8. The polymer of claim 6 , having the following formula (VI):
wherein:
R 3 represents an aliphatic or aromatic chain, optionally substituted by one or several functional groups and/or optionally interrupted by one or several oxygen atoms;
R 4 represents a group —S—C(═S)—Z, Z being the group controlling the reactivity of the C═S bond;
q is comprised from 2 to 100; and
r is comprised from 2 to 100.
9. The polymer of claim 1 , having the following formula (VII):
wherein:
L, R 2 , X − , m, and n are as defined in claim 1 , and
q is comprised from 2 to 100.
10. The polymer of claim 1 , having the following formula (VIII):
wherein:
X − and n are as defined in claim 1 ; and
q is comprised from 2 to 100.
11. A method for the preparation of a polymer of claim 1 , comprising a step of RAFT polymerization of a monomer having the following formula (IX):
wherein R 1 , L, R 2 , X − , m, and n are as defined in claim 1 .
12. The method of claim 11 , wherein m is 0, and comprising a step of RAFT polymerization of monomers having the following formulae (X) and (XI):
wherein p is an integer comprised from 1 to 10.
13. A monomer having one of the following formulae (IX) or (X):
wherein R 1 , L, R 2 , X − , m, and n are as defined in claim 1 .
14. A method for delivering a drug to a subject in need thereof, comprising
encapsulating the drug with the polymer of claim 1 , and
delivering the drug to the subject.
15. A method for treating a bacterial infection in a patient in need thereof, comprising
administering to the patient a pharmaceutically acceptable amount of the polymer of claim 1 .