Compositions and kits pertaining to analyte determination

• US 7,195,751 B2
• Filed: 01/27/2004
• Issued: 03/27/2007
• Est. Priority Date: 01/30/2003
• Status: Expired due to Term

• Current Assignee: DH Technologies Pte. Ltd. (Danaher Corporation)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Bartlet-Jones, Michael, Pappin, Darryl J. C.
• Primary Examiner(s): McKane; Joseph K.
• Assistant Examiner(s): GRAZIER, NYEEMAH A
• Application Number:
  US10/765,267
• Publication Number:
  US 20040220412A1
• Time in Patent Office: 1,155 Days
• Field of Search: 544/64, 544/112, 544/141, 544/172, 544/372, 544/399, 546/2, 546/208, 546/238, 424/1.37, 424/1.81, 435/6, 435/23
• US Class Current: 424/1.81
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: G01N 2458/15 Non-radioactive isotope labels, e.g. for detection by mass spectrometry
• CPC Class Codes: G01N 33/532 Production of labelled immunochemicals
• CPC Class Codes: G01N 33/6842 Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/145555 Hetero-N
• CPC Class Codes: Y10T 436/147777 Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

This invention pertains to methods, mixtures, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.

Claims

1. A compound of formula:

2. The compound of claim 1, wherein the compound is isotopically enriched with three or more heavy atom isotopes.

3. The compound of claim 1, wherein the six-membered heterocydlic ring is substituted with one or more substituents.

4. The compound of claim 3, wherein the one or more substituents are alkyl, alkoxy or aryl groups.

5. The compound of claim 1, wherein LG is N-hydroxysuccinimide.

6. The compound of claim 1, wherein the compound is a salt.

7. The compound of claim 1, wherein the compound is a mono-TFA salt, a mono-HCl salt, a bis-TFA salt or a bis-HCl salt.

8. The compound of claim 1, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

9. The compound of claim 1, wherein each incorporated heavy atom isotope is present in at least 93 percent isotopic purity.

10. The compound of claim 1, wherein each incorporated heavy atom isotope is present in at least 96 percent isotopic purity.

11. A method comprising:

a) reacting an analyte with the compound of claim 1 to thereby produce a labeled analyte; and

b) mixing the labeled analyte with one or more differentially labeled analytes.

12. The compound of claim 1 of the formula:

13. The compound of claim 1 of the formula:

14. An N-substituted morpholine acetic acid active ester compound of the formula:

15. The compound of claim 14, wherein the N-substituted morpholine acetic acid active ester is isotopically enriched with three or more heavy atom isotopes.

16. The compound of claim 14, wherein LG is N-hydroxysuccinimide.

17. The compound of claim 14, wherein each Z′

is independently hydrogen, deuterium, fluorine, chlorine, bromine or iodine.

18. The compound of claim 14, wherein each Z′

is independently hydrogen or methyl.

19. The compound of claim 14, wherein X′

is ¹⁶O or ¹⁸O.

20. The compound of claim 14, wherein the nitrogen atom of the morpholine ring is ¹⁴N or ¹⁵N.

21. The compound of claim 14, of the formula:

22. The compound of claim 14, wherein the compound is a mono-TFA salt or a mono-HCl salt.

23. The compound of claim 14, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

24. The compound of claim 14, wherein each incorporated heavy atom isotope is present in at least 93 percent or isotopic purity.

25. The compound of claim 14, wherein each incorporated heavy atom isotope is present in at least 96 percent or isotopic purity.

26. An N-substituted piperidine acetic add active ester compound of the formula:

27. The compound of claim 26, wherein the N-substituted piperidine acetic acid active ester is isotopically enriched with three or more heavy atom isotopes.

28. The compound of claim 26, wherein LG is N-hydroxysuccinimide.

29. The compound of claim 26, wherein each Z′

is independently hydrogen, deuterium, fluorine, chlorine, bromine or iodine.

30. The compound of claim 26, wherein each Z′

is independently hydrogen or methyl.

31. The compound of claim 26, wherein X′

is ¹⁶O or ¹⁶O.

32. The compound of claim 26, wherein the nitrogen atom of the piperidine ring is ¹⁴N or ¹⁵N.

33. The compound of claim 26, of the formula:

34. The compound of claim 26, wherein the compound is a mono-TFA salt or a mono-HCl salt.

35. The compound of claim 26, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

36. The compound of claim 26, wherein each incorporated heavy atom isotope is present in at least 93 percent or isotopic purity.

37. The compound of claim 26, wherein each incorporated heavy atom isotope is present in at least 96 percent or isotopic purity.

38. An N-substituted piperazine acetic acid active ester compound of the formula:

39. The compound of claim 38, wherein the N-substituted piperazine acetic add active ester is isotopically enriched with three or more heavy atom isotopes.

40. The compound of claim 38, wherein LG is N-hydroxysuccinimide.

41. The compound of claim 38, wherein each Z′

is independently hydrogen, deuterium, fluorine, chlorine, bromine or iodine.

42. The compound of claim 38, wherein each Z′

is independently hydrogen or methyl.

43. The compound of claim 38, wherein X′

is ¹⁶O or ¹⁸O.

44. The compound of claim 38, wherein each nitrogen atom of the piperazine ring is ¹⁴N or ¹⁵N.

45. The compound of claim 38, of the formula:

46. The compound of claim 38, wherein the compound is a mono-TFA salt, a mono-HCl salt, a bis-TFA salt or a bis-HCl salt.

47. The compound of claim 38, wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.

48. The compound of claim 38, wherein each incorporated heavy atom isotope is present in at least 93 percent or isotopic purity.

49. The compound of claim 38, wherein each incorporated heavy atom isotope is present in at least 96 percent or isotopic purity.