Claims
- 1. A branched reactive polymer having the structure:
- 2. The branched polymer of claim 1, wherein X′ is —NH—, —O— or —S—.
- 3. The branched polymer of claim 1, wherein q is 2 to about 5.
- 4. The branched polymer of claim 1, wherein the POLY polymer arms are symmetrically located on the aliphatic hydrocarbon.
- 5. The branched polymer of claim 1, wherein R comprises from 3 to about 7 carbon atoms.
- 6. The branched polymer of claim 1, wherein R comprises three carbon atoms.
- 7. The branched polymer of claim 1, wherein each POLY polymer arm and the Y functional group are attached to different carbon atoms of R.
- 8. The branched polymer of claim 1, wherein each POLY has the structure Z-POLY-, wherein Z is a capping group or a functional group.
- 9. The branched polymer of claim 8, wherein each Z is a capping group independently selected from the group consisting of alkoxy, alkyl, benzyl, aryl, and aryloxy.
- 10. The branched polymer of claim 8, wherein each Z is methoxy.
- 11. The branched polymer of claim 8, wherein each Z is a functional group independently selected from the group consisting of hydroxyl, active ester, active carbonate, acetal, aldehyde, aldehyde hydrate, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, hydrazide, thiol, alkanoic acid, acid halide, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxal, dione, mesylate, tosylate, and tresylate.
- 12. The branched polymer of claim 1, wherein Y selected from the group consisting of hydroxyl, active ester, active carbonate, acetal, aldehyde, aldehyde hydrate, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, hydrazide, thiol, alkanoic acid, acid halide, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxal, dione, mesylate, tosylate, and tresylate.
- 13. The branched polymer of claim 1, wherein each POLY is independently selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrrolidone), poly(hydroxyalkylmethacrylamide), poly(hydroxyalkylmethacrylate), poly(saccharides), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, poly(N-acryloylmorpholine), and copolymers, terpolymers, and mixtures thereof.
- 14. The branched polymer of claim 1, wherein each POLY is poly(ethylene glycol).
- 15. The branched polymer of claim 1, wherein each POLY is linear or branched.
- 16. The branched polymer of claim 1, wherein p is 1 and X is selected from the group consisting of a heteroatom, -alkylene-, —O-alkylene-O—, -alkylene-O-alkylene-, -aryl-O—, —O-aryl-, (—O-alkylene-)m, and (-alkylene-O—)m, wherein m is 1-10.
- 17. The branched polymer of claim 1, wherein p is 0 and Y is hydroxyl.
- 18. The branched polymer of claim 1, wherein Y is protected hydroxyl having the structure —O-Gp, wherein Gp is a protecting group.
- 19. The branched polymer of claim 18, wherein Gp is selected from the group consisting of benzyl, acetal and dihydropyranyl.
- 20. The branched polymer of claim 1, having the structure:
- 21. A biologically active conjugate, comprising a biologically active molecule covalently attached to a branched reactive polymer of claim 1.
- 22. A biologically active conjugate comprising a branched polymer covalently attached to a biologically active molecule, wherein the conjugate has the structure:
- 23. The biologically active conjugate of claim 22, wherein D is selected from the group consisting of peptides, proteins, enzymes, small molecule drugs, dyes, lipids, nucleosides, nucleotides, oligonucleotides, polynucleotides, nucleic acids, polysaccharides, steroids, cells, viruses, liposomes, microparticles, micelles, fats, and electrolytes.
- 24. The biologically active conjugate of claim 22, having the structure:
- 25. A nucleophile-substituted aliphatic hydrocarbon core molecule having the structure:
- 26. The aliphatic hydrocarbon of claim 25, wherein each Nu is amino, thiol, or hydroxyl.
- 27. The aliphatic hydrocarbon of claim 25, wherein Y′ is a protected hydroxyl.
- 28. The aliphatic hydrocarbon of claim 25, having the structure:
- 29. A method of preparing a branched poly(alkylene glycol) polymer, comprising:
providing an aliphatic hydrocarbon substituted with at least two nucleophilic groups and at least one protected functional group; polymerizing alkylene oxide monomer units onto the aliphatic hydrocarbon at the site of the nucleophilic groups to form at least two poly(alkylene glycol) polymers attached to the aliphatic hydrocarbon via heteroatom linkages; end-capping the poly(alkylene glycol) polymers with an alkyl group to form alkoxy-terminated polymers; and deprotecting the protected functional group to form a hydroxyl group.
- 30. The method of claim 29, wherein the aliphatic hydrocarbon has the structure:
- 31. The method of claim 29, wherein the alkylene oxide monomer units are units of ethylene oxide.
- 32. The method of claim 29, wherein the protected functional group is a protected hydroxyl group and said deprotecting step comprises hydrolysis or hydrogenolysis of the protected hydroxyl group.
- 33. The method of claim 29, wherein said end-capping step comprises end-capping the polymers with methoxy.
- 34. The method of claim 29, wherein the aliphatic hydrocarbon is selected from the group consisting of 2-benzyloxy-1,3-propanediol, 2-benzyloxyethoxy-1,3-propanediol, and 2-benzyloxyethoxyethyl-1,3-propanediol.
- 35. The method of claim 29, further comprising modifying the deprotected functional group to form a second functional group.
- 36. The method of claim 35, wherein the second functional group is selected from the group consisting of active ester, active carbonate, acetal, aldehyde, aldehyde hydrate, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, hydrazide, thiol, alkanoic acid, acid halide, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxal, dione, mesylate, tosylate, and tresylate.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority of U.S. Provisional Application Serial No. 60/337,613, filed Nov. 7, 2001, which is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60337613 |
Nov 2001 |
US |