Carbohydrate-based drug delivery polymers and conjugates thereof
View Patent ↗Provided herein are water-soluble carbohydrate polymers which are monoderivatized at their reducing terminus, such that the carbohydrate polymers can be selectively conjugated at a single location. Also provided are methods of preparation and conjugation of the monoderivatized carbohydrate polymers.
1. A conjugate comprising a monofunctional water-soluble carbohydrate-based reagent conjugated to a biologically active molecule (B), wherein the conjugate has a structure selected from
where:
POLY 1 is a dextran polymer; and
G 2 is covalent bond comprising a residue or converted form of an aldehyde, a carboxylic acid or a carboxylic acid derivative, in each case following a reaction with a corresponding functional group on biologically active molecule (B).
2. The conjugate of claim 1 , wherein POLY 1 has a molecular weight of 200 Da to 2,000,000 Da.
3. The conjugate of claim 1 , wherein POLY 1 has a molecular weight of 5,000 Da to 70,000 Da.
4. The conjugate of claim 1 , wherein POLY 1 has a molecular weight selected from of about 5,000 Da, about 10,000 Da, about 20,000 Da, about 40,000 Da, and about 70,000 Da.
5. The conjugate of claim 1 , wherein the reagent has the structure
where POLY 1 is a dextran polymer having a molecular weight of 200 Da to 2,000,000 Da.
6. The conjugate of claim 5 , wherein POLY 1 has a molecular weight of 5,000 Da to 70,000 Da.
7. The conjugate of claim 5 , wherein POLY 1 has a molecular weight of about 20,000 Da.
8. The conjugate of claim 5 , wherein POLY 1 has a molecular weight of about 40,000 Da.
9. The conjugate of claim 1 , wherein the reagent has the structure
where POLY 1 is a dextran polymer having a molecular weight of 200 Da to 2,000,000 Da.
10. The conjugate of claim 9 , wherein POLY 1 has a molecular weight of 5,000 Da to 70,000 Da.
11. The conjugate of claim 9 , wherein POLY 1 has a molecular weight of about 20,000 Da.
12. The conjugate of claim 9 , wherein POLY 1 has a molecular weight of about 40,000 Da.
13. The conjugate of claim 1 , wherein the reagent has the structure
where POLY 1 is a dextran polymer having a molecular weight of 200 Da to 2,000,000 Da.
14. The conjugate of claim 13 , wherein POLY 1 has a molecular weight of 5,000 Da to 70,000 Da.
15. The conjugate of claim 13 , wherein POLY 1 has a molecular weight of about 20,000 Da.
16. The conjugate of claim 13 , wherein POLY 1 has a molecular weight of about 40,000 Da.
17. The conjugate of claim 1 , wherein the biologically active molecule is selected from small molecules, peptides, polypeptides, and proteins.
18. The conjugate of claim 17 , wherein the biologically active molecule has at least one reactive amino group.
19. The conjugate of claim 17 , wherein the biologically active molecule is selected from protegrin-1, C-peptide, and insulin.