Granted Patent B2

US 12,258,430 · App. 17/206,050 · Granted Mar 25, 2025

Inventors: Hua Wang (Cambridge, MA); David J. Mooney (Cambridge, MA)

Assignee: President and Fellows of Harvard College

C08F251/00A61K39/0011A61K49/221A61K49/222A61N7/00A61P35/00C08B37/0006G01N33/54346G01N33/548A61N2007/0004C08F2438/03

Abstract

Claims (47)

1. A click functionalized polysaccharide polymer which is a product of radical-catalyzed polymerization;

wherein said radical-catalyzed polymerization involves a reaction between one or more saccharide monomers;

wherein each saccharide monomer comprises a saccharide molecule; a click reagent attached to said saccharide molecule; and a moiety comprising a functional group amenable to radical polymerization attached to said saccharide molecule; and

wherein:

(i) said saccharide molecule further comprises one or more hydrolysable substituents at the C1 position, the C3 position, the C4 position or C5 position, and wherein at least one of said hydrolysable substituent is represented by formula (1):

wherein R is alkyl;

(ii) said moiety comprising a functional group amenable to radical polymerization is attached to said saccharide molecule at the C1 position;

(iii) said moiety comprising a functional group amenable to radical polymerization comprises an acrylate or methacrylate; and/or

(iv) said radical-catalyzed polymerization is reversible addition-fragmentation chain transfer (RAFT) polymerization involving the use of a RAFT agent; and wherein said RAFT agent comprises a thiocarbonate moiety, a dithiocarbamate moiety or a dithiobenzoate moiety.

2. The polymer of claim 1 , wherein:

(i) said saccharide molecule is selected from the group consisting of mannose, galactose, fucose and sialic acid;

(ii) said click reagent is attached to said saccharide molecule at the C2 position; and/or

(iii) said polymer comprises 10 to 1000 saccharide units.

3. The polymer of claim 2 , wherein said saccharide molecule is mannose.

4. The polymer of claim 2 , wherein said click reagent is selected from the group consisting of azide, dibenzocyclooctyne (DBCO), transcyclooctene, tetrazine and norbornene and variants thereof.

5. The polymer of claim 4 , wherein said click reagent is azide.

6. The polymer of claim 1 , wherein:

(i) said moiety comprising a functional group amenable to radical polymerization is attached to said saccharide molecule at the C1 position; and/or

(ii) said moiety comprising a functional group amenable to radical polymerization comprises an acrylate or methacrylate.

7. The polymer of claim 1 , wherein said saccharide molecule further comprises one or more hydrolysable substituents at the C1 position, the C3 position, the C4 position or C5 position, and wherein said hydrolysable substituent is represented by formula (1):

wherein R is alkyl.

8. The polymer of claim 7 , wherein R is methyl.

9. The polymer of claim 1 , wherein said radical-catalyzed polymerization is reversible addition-fragmentation chain transfer (RAFT) polymerization involving the use of a RAFT agent; and wherein said RAFT agent comprises a thiocarbonate moiety, a dithiocarbamate moiety or a dithiobenzoate moiety.

10. The polymer of claim 9 , wherein said RAFT agent comprises a thiocarbonate moiety.

11. The polymer of claim 10 , wherein said RAFT agent comprises 2-(dodecylthiocarbonothioylthio)-2-methylpropionate or poly(ethylene glycol)methyl ether 2-(dodecylthiocarbonothioylthio)-2-methylpropionate.

12. The polymer of claim 1 comprising 20 to 500, 100 to 500 or 200 to 600 saccharide units.

13. The polymer of claim 1 comprising:

(i) the structure of formula (2):

 wherein n is a number between 10 and 1000;

(ii) the structure of formula (3):

 wherein n is a number between 10 and 1000; and m is a number between 45 and 200; or

(iii) the structure of formula (4):

 wherein n is a number between 10 and 1000; and m is a number between 45 and 200.

14. A click-functionalized amphiphilic polymer which is a product of radical-catalyzed polymerization;

wherein said radical-catalyzed polymerization involves a reaction between a reagent comprising a hydrophilic portion and one or more saccharide monomers;

wherein each saccharide monomer comprises a saccharide molecule; a click reagent attached to said saccharide molecule; and a moiety comprising a functional group amenable to radical polymerization attached to said saccharide molecule; and

wherein:

(i) said saccharide molecule further comprises one or more hydrolysable substituents at the C1 position, the C3 position, the C4 position or C5 position, and wherein at least one of said hydrolysable substituent is represented by formula (1);

wherein R is alkyl;

(ii) said moiety comprising a functional group amenable to radical polymerization is attached to said saccharide molecule at the C1 position;

(iii) said moiety comprising a functional group amenable to radical polymerization comprises an acrylate or methacrylate;

(iv) said radical-catalyzed polymerization is reversible addition-fragmentation chain transfer (RAFT) polymerization involving the use of a RAFT agent; and wherein said RAFT agent comprises a thiocarbonate moiety, a dithiocarbamate moiety or a dithiobenzoate moiety; and/or

(v) said hydrophilic portion comprises a hydrophilic polymer comprising polyethylene oxide (PEG), and wherein said PEG comprises between 20 and 450 PEG units.

15. The polymer of claim 14 , wherein said hydrophilic polymer is polyethylene oxide (PEG).

16. The polymer of claim 15 , wherein said PEG comprises between 20 and 450 PEG units.

17. A nanoparticle for labeling cells with a click reagent comprising the polymer of claim 1 .

18. An in vitro method of labeling a cell with a click chemistry reagent, comprising contacting the cell with the polymer of claim 1 .

Assignments (2)

Continuity (3)

References Cited (400)