Enzyme-mimicking polymers

• US 20030186330A1
• Filed: 03/12/2003
• Published: 10/02/2003
• Est. Priority Date: 09/12/2000
• Status: Active Grant

• Current Assignee: Koji Sode
• Original Assignee: Koji Sode
• Inventors: Sode, Koji
• Granted Patent: US 7,232,861 B2
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: G01N 33/723 Glycosylated haemoglobin

Abstract

The present invention provides synthetic polymers having novel catalytic functions which mimic enzymatic reactions. The invention also provides a method for measuring glycated proteins such as glycated hemoglobin (HbA1c) and glycated albumin and for measuring their decomposition products fructosylamines, such as fructosylvaline, as well as assay reagents and sensors for use in the method.

Claims

1. A synthetic polymer capable of binding to fructosylamine and catalyzing oxidation of the fructosylamine in the presence of an electron acceptor.

2. The polymer according to claim 1, comprising a boronic acid group.

3. The polymer according to claim 1, comprising an imidazole group.

4. The polymer according to claim 1, comprising both of imidazole and boronic acid groups.

5. The polymer according to claim 1, obtained by polymerizing vinylboronic acid.

7. The polymer according to any one of claims 1 to 6, which is a copolymer of vinylimidazole and vinylboronic acid.

8. The polymer according to any one of claims 1 to 7, obtained by synthesizing the polymer using 1-vinylimidazole.

9. The polymer according to any one of claims 1 to 8, obtained by synthesizing the polymer using 4-vinylphenylboronic acid.

10. The polymer according to any one of claims 1 to 9, obtained by synthesizing the polymer in the presence of a crosslinking reagent.

11. The polymer according to claim 10 wherein the crosslinking reagent is ethylene glycol dimethacrylate.

12. The polymer according to any one of claims 1 to 11, obtained by synthesizing the polymer using a template molecule.

13. The polymer according to claim 12, obtained by removing the template molecule after polymerization.

14. The polymer according to claim 12 or 13 wherein the template molecule is fructosylamine.

15. The polymer according to claim 14 wherein the fructosylamine is fructosylvaline.

16. The polymer according to claim 12 or 13 wherein the template molecule is methylvaline.

17. The polymer according to any one of claims 1 to 11, obtained by synthesizing the polymer in the presence of a basic monomer.

19. A method for assaying fructosylamine in a sample, comprising contacting the with the polymer as claimed in any one of claims 1 to A3, and measuring the amount of an oxidized form of fructosylamine.

20. The method according to claim 19 wherein the sample is contacted with the polymer in the presence of a mediator, and the amount of reduced mediator formed by oxidation of the fructosylamine is electrochemically determined.

21. The method according to claim 19 or 20 wherein the sample is contacted with the polymer in a reaction solution at pH 6 to 10.

22. A fructosylamine assay kit comprising the polymer as claimed in any one of claims 1 to 18.

23. A fructosylamine sensor comprising the polymer as claimed in any one of claims 1 to 18.

24. The fructosylamine sensor according to claim 23, comprising a carbon paste electrode.

25. A method for assaying glycated hemoglobin (HbA1c), comprising measuring the amount of HbA1c or fructosylvaline formed by decomposition of HbA1c in a sample by the method of claim 19.

26. A glycated hemoglobin assay kit comprising the polymer as claimed in any one of claims 1 to 18.

27. A glycated hemoglobin sensor comprising the polymer as claimed in any one of claims 1 to 18.

28. A method for assaying glycated albumin, comprising measuring the amount of glycated albumin or fructosylamine generated by decomposition of the glycated albumin in a sample by the method of claim 19.

29. A glycated albumin assay kit comprising the polymer as calmed in any one of claims 1 to 18.

30. A glycated albumin sensor comprising the polymer as calmed in any one of claims 1 to 18.

6. The polymer according to any one of clams 1 to 5, obtained by synthesizing the polymer using a compound containing a vinylimidazole group.

18. The polymer according to claim A2, wherein the basic monomer is selected from the group consisting of allylamine, N,N′

-dimethylaminoethyl methacrylate, dimethylaminopropyl methacrylate, and diethylaminoethyl methacrylate.

31. A method for producing a synthetic polymer capable of binding to fructosylamine and catalyzing oxidation of the fructosylamine in the presence of an electron acceptor, said method comprising polymerizing vinylboronic acid.

35. The method according to any one of claims 31 to 34 wherein a crosslinking reagent is further added to the polymerization reaction.

36. The method according to claim 35 wherein the crosslinking reagent is ethylene glycol dimethacrylate.

37. The method according to any one of claims 31 to 36 wherein a template molecule is further added to the polymerization reaction.

38. The method according to claim 37, further comprising the step of removing the template molecule after polymerization.

39. The method according to claim 37 or 38 wherein the template molecule is fructosylamine.

40. The method according to claim 39 wherein the fructosylamine is fructosylvaline.

41. The method according to claim 37 or 38 wherein the template molecule is methylamine.

42. The method according to claim 41 wherein the methylamine is methylvaline.

43. The method according to any one of claims 31 to 36 wherein a basic monomer is further added to the polymerization reaction.

44. The method according to claim 43 wherein the basic monomer is selected from the group consisting of allylamine, N,N′

-dimethylaminoethyl methacrylate, dimethylaminopropyl methacrylate, and diethylaminoethyl methacrylate.

32. A method for producing a synthetic polymer capable of binding to fructosylamine and catalyzing oxidation of the fructosylamine in the presence of an electron acceptor, said method comprising copolymerizing vinylimidazole and vinylboronic acid.

34. The method according to claim 32 or 33 wherein the vinylimidazole is 1-vinylimidazole.

33. A method for producing a synthetic polymer capable of binding to fructosylamine and catalyzing oxidation of the fructosylamine in the presence of an electron acceptor, said method comprising copolymerizing vinylimidazole and 4-vinylphenylboronic acid.