Substituted polyesters by thiol-ene modification: rapid diversification for therapeutic protein stabilization

1. A biodegradable trehalose or zwitterion polymer, wherein the polymer consists of the general structure:

R′-[DG-CR 1 R 2 —CR 3 R 4 —CR 5 R 6 —CR 7 R 8 —CR 9 R 10 ] m —R″

wherein R 1 -R 10 are independently selected from hydrogen or a side chain comprising at least one carbon atom, and wherein at least one of R 1 -R 10 is a side chain comprising trehalose, -L-trehalose, -zwitterion or -L-zwitterion, wherein L is a linker molecule that links trehalose or zwitterion to the polymer through the reaction of at least one of the trehalose hydroxyl groups (—OH) or through one end of the zwitterion, wherein DG is a biodegradable group, and

wherein R′ and R″ are end groups, and

wherein m≥1.

2. The polymer of claim 1 , wherein R′ and R″ are independently comprising —H, —Alkyl, -Alkenyl, -Alkynyl, -Aryl, disulfide, pyridyl disulfide, 5-thio-2-nitrobenzoic acid, disulfide reductants, Michael acceptors, maleimides, maleimide derivatives, dihalomaleimides, vinyl groups, vinyl sulfones, acryloyl derivatives, haloacetyl, alkyl halide derivatives, aziridines, arylating agents, isothiocyanates, isocyanates, acryl azides, activated esters, N-hydroxysuccinimide esters, para-nitrophenyl esters, sulfonyl chlorides, aldehydes and glyoxals (with or without reductive amination), epoxides (also called oxiranes), carbonates, arylating agents, imidoesters, carbodiimides, anhydrides, primary amines, secondary amines, tertiary amines, diazoalkanes, diazoacetyls, carbonyldiimidazoles, carbonates, chloroformates, alkyl halogens, isocyanates, aminooxy (hydroxylamines), hydrazines, azide or biomolecules.

3. The polymer of claim 1 , wherein R′ and R″ are independently comprising —H, -Alkyl, -Alkenyl, -Alkynyl, azide or biomolecules.

4. The polymer of claim 1 , wherein DG comprises at least one ester group.

5. The polymer of claim 1 , wherein DG is an ester group in the backbone of the polymer.

6. The polymer of claim 1 , the linking molecules L are methylene groups —(CH 2 ) n — (n=1-1000).

7. The polymer of claim 6 , wherein the linking molecules L are methylene groups —(CH 2 ) n — (n=1-10).

8. The polymer of claim 1 , wherein the polymer is

wherein n=1-10000.

9. The polymer of claim 1 , wherein the polymer is

wherein n=1-10000.

10. A biodegradable trehalose or zwitterion polymer, wherein the polymer consists of the general structure: R′—[OOC—CR 1 R 2 —(CH 2 ) m ] n —OR″,

wherein m=0-10, n=1-10000 and R 1 and R 2 are independently selected from hydrogen or a side chain comprising at least one carbon atom, wherein at least one of R 1 and R 2 is a side chain comprising -trehalose, -L-trehalose, -zwitterion or -L-zwitterion, wherein L is a linker molecule that links the trehalose or zwitterion to the polymer through the reaction of at least one of the trehalose hydroxyl groups (—OH) or through one end of the zwitterion,

wherein R′ and R″ are end groups.

11. The polymer of claim 10 , wherein R′ and R″ are independently comprising —H, -Alkyl, -Alkenyl, -Alkynyl, -Aryl, disulfide, pyridyl disulfide, 5-thio-2-nitrobenzoic acid, disulfide reductants, Michael acceptors, maleimides, maleimide derivatives, dihalomaleimides, vinyl groups, vinyl sulfones, acryloyl derivatives, haloacetyl, alkyl halide derivatives, aziridines, arylating agents, isothiocyanates, isocyanates, acryl azides, activated esters, N-hydroxysuccinimide esters, para-nitrophenyl esters, sulfonyl chlorides, aldehydes and glyoxals (with or without reductive amination), epoxides (also called oxiranes), carbonates, arylating agents, imidoesters, carbodiimides, anhydrides, primary amines, secondary amines, tertiary amines, diazoalkanes, diazoacetyls, carbonyldiimidazoles, carbonates, chloroformates, alkyl halogens, isocyanates, aminooxy (hydroxylamines), hydrazines, azide or biomolecules.

12. The polymer of claim 10 , wherein R′ and R″ are independently comprising —H, -Alkyl, -Alkenyl, -Alkynyl, azide or biomolecules.

13. The polymer of claim 10 , the linking molecules L are methylene groups —(CH 2 ) n — (n=1-1000).

14. The polymer of claim 13 , wherein the linking molecules L are methylene groups —(CH 2 ) n — (n=1-10).

15. A biodegradable zwitterion polymer, wherein the polymer consists of the general structure: R—[OOC—CR 1 R 2 —(CH 2 ) m ] n —OR″,

wherein m=0-10, n=1-10000 and R 1 and R 2 are independently selected from hydrogen or a side chain comprising at least one carbon atom, wherein at least one of R 1 and R 2 is a side chain comprising -zwitterion or -L-zwitterion, wherein L is a linker molecule that links zwitterion to the polymer through one end of the zwitterion electrical charges,

wherein R′ and R″ are end groups.

16. The polymer of claim 15 , wherein R′ and R″ are independently comprising —H, -Alkyl, -Alkenyl, -Alkynyl, -Aryl, disulfide, pyridyl disulfide, 5-thio-2-nitrobenzoic acid, disulfide reductants, Michael acceptors, maleimides, maleimide derivatives, dihalomaleimides, vinyl groups, vinyl sulfones, acryloyl derivatives, haloacetyl, alkyl halide derivatives, aziridines, arylating agents, isothiocyanates, isocyanates, acryl azides, activated esters, N-hydroxysuccinimide esters, para-nitrophenyl esters, sulfonyl chlorides, aldehydes and glyoxals (with or without reductive amination), epoxides (also called oxiranes), carbonates, arylating agents, imidoesters, carbodiimides, anhydrides, primary amines, secondary amines, tertiary amines, diazoalkanes, diazoacetyls, carbonyldiimidazoles, carbonates, chloroformates, alkyl halogens, isocyanates, aminooxy (hydroxylamines), hydrazines, azide or biomolecules.

17. The polymer of claim 15 , wherein R′ and R″ are independently comprising —H, -Alkyl, -Alkenyl, -Alkynyl, azide or biomolecules.

18. The polymer of claim 15 , the linking molecules L are methylene groups —(CH 2 ) n — (n=1-1000).

19. The polymer of claim 18 , wherein the linking molecules L are methylene groups —(CH 2 ) n — (n=1-10).

20. The polymer of claim 15 , where the zwitterion is an amino acid derivative.