Nucleic acid labeling compounds

US 20020165372A1
Filed: 09/11/2001
Published: 11/07/2002
Est. Priority Date: 01/23/1996
Status: Active Grant

First Claim

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1. A nucleic acid labeling compound of the following structure:

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Abstract

Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Citations

171 Claims

1. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 45, 63)
- - 2. A nucleic acid labeling compound according to claim 1, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      C(O)NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or a carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 3. A nucleic acid labeling compound according to claim 2, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 4. A nucleic acid labeling compound according to claim 2, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 5. A nucleic acid labeling compound according to claim 2, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 6. A nucleic acid labeling compound according to claim 2, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 7. A nucleic acid labeling compound according to claim 2, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 8. A nucleic acid labeling compound according to claim 2, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 45. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 2 with a nucleic acid.
  - 63. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 2 to a nucleic acid.

9. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 46, 64)
- - 10. A nucleic acid labeling compound according to claim 9, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 11. A nucleic acid labeling compound according to claim 10, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 12. A nucleic acid labeling compound according to claim 10, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 13. A nucleic acid labeling compound according to claim 10, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 14. A nucleic acid labeling compound according to claim 10, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 15. A nucleic acid labeling compound according to claim 10, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 16. A nucleic acid labeling compound according to claim 10, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 17. A nucleic acid labeling compound according to claim 9, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 2.
  - 18. A nucleic acid labeling compound according to claim 9, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 2.
  - 19. A nucleic acid labeling compound according to claim 10, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 20. A nucleic acid labeling compound according to claim 10, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 46. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 10 with a nucleic acid.
  - 64. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 10 to a nucleic acid.

21. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 47, 48, 49, 65, 66, 67, 70)
- - 22. A nucleic acid labeling compound according to claim 21, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      C≡
      
      C(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 23. A nucleic acid labeling compound according to claim 22, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 1.
  - 24. A nucleic acid labeling compound according to claim 22, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C≡
      
      —
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 1.
  - 25. A nucleic acid labeling compound according to claim 22, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 26. A nucleic acid labeling compound according to claim 22, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 27. A nucleic acid labeling compound according to claim 22, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 28. A nucleic acid labeling compound according to claim 22, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 30. A nucleic acid labeling compound according to claim 29, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      NH(CH₂)_nNNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 31. A nucleic acid labeling compound according to claim 30, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1.
  - 32. A nucleic acid labeling compound according to claim 30, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1.
  - 33. A nucleic acid labeling compound according to claim 30, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 34. A nucleic acid labeling compound according to claim 30, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 35. A nucleic acid labeling compound according to claim 30, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 36. A nucleic acid labeling compound according to claim 30, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 38. A nucleic acid labeling compound according to claim 37, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      CH═
      
      CH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 39. A nucleic acid labeling compound according to claim 38, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 40. A nucleic acid labeling compound according to claim 38, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 47. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 22 with a nucleic acid.
  - 48. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 30 with a nucleic acid.
  - 49. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 38 with a nucleic acid.
  - 65. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 22 to a nucleic acid.
  - 66. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 30 to a nucleic acid.
  - 67. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 38 to a nucleic acid.
  - 70. A method according to claim 69, wherein the probe is attached to a glass chip.

29. A nucleic acid labeling compound of the following structure:

37. A nucleic acid labeling compound of t he following structure:

41. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (42, 43, 44, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 68, 69, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80)
- - 42. A nucleic acid labeling compound according to claim 41, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      CH═
      
      CH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 43. A nucleic acid labeling compound according to claim 42, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 44. A nucleic acid labeling compound according to claim 42, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 50. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 42 with a nucleic acid.
  - 51. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 45 bound to a complementary probe.
  - 52. The hybridization product according to claim 51, wherein the probe is attached to a glass chip.
  - 53. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 46 bound to a complementary probe.
  - 54. The hybridization product according to claim 53, wherein the probe is attached to a glass chip.
  - 55. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 47 bound to a complementary probe.
  - 56. The hybridization product according to claim 55, wherein the probe is attached to a glass chip.
  - 57. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 48 bound to a complementary probe.
  - 58. The hybridization product according to claim 57, wherein the probe is attached to a glass chip.
  - 59. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 49 bound to a complementary probe.
  - 60. The hybridization product according to claim 59, wherein the probe is attached to a glass chip.
  - 61. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 50 bound to a complementary probe.
  - 62. The hybridization product according to claim 61, wherein the probe is attached to a glass chip.
  - 68. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 42 to a nucleic acid.
  - 69. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 45 with a probe.
  - 71. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 46 with a probe.
  - 72. A method according to claim 71, wherein the probe is attached to a glass chip.
  - 73. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 47 with a probe.
  - 74. A method according to claim 73, wherein the probe is attached to a glass chip.
  - 75. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 48 with a probe.
  - 76. A method according to claim 75, wherein the probe is attached to a glass chip.
  - 77. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 49 with a probe.
  - 78. A method according to claim 77, wherein the probe is attached to a glass chip.
  - 79. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 50 with a probe.
  - 80. A method according to claim 79, wherein the probe is attached to a glass chip.

81. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (82, 83, 84, 85, 86, 87, 88, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100)
- - 82. A nucleic acid labeling compound according to claim 81, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      C(O)NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or a carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 83. A nucleic acid labeling compound according to claim 82, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 84. A nucleic acid labeling compound according to claim 82, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 85. A nucleic acid labeling compound according to claim 82, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 86. A nucleic acid labeling compound according to claim 82, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 87. A nucleic acid labeling compound according to claim 82, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 88. A nucleic acid labeling compound according to claim 82, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 90. A nucleic acid labeling compound according to claim 89, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 91. A nucleic acid labeling compound according to claim 90, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 92. A nucleic acid labeling compound according to claim 90, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 93. A nucleic acid labeling compound according to claim 90, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 94. A nucleic acid labeling compound according to claim 90, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 95. A nucleic acid labeling compound according to claim 90, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 96. A nucleic acid labeling compound according to claim 90, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 97. A nucleic acid labeling compound according to claim 89, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 2.
  - 98. A nucleic acid labeling compound according to claim 89, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 2.
  - 99. A nucleic acid labeling compound according to claim 90, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 100. A nucleic acid labeling compound according to claim 90, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.

89. A nucleic acid labeling compound of the following structure:

101. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (102, 103, 104, 105, 106, 107, 108)
- - 102. A nucleic acid labeling compound according to claim 101, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      C≡
      
      C(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 103. A nucleic acid labeling compound according to claim 102, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 1.
  - 104. A nucleic acid labeling compound according to claim 102, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 1.
  - 105. A nucleic acid labeling compound according to claim 102, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      CH≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 106. A nucleic acid labeling compound according to claim 102, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 107. A nucleic acid labeling compound according to claim 102, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 108. A nucleic acid labeling compound according to claim 102, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.

109. A nucleic acid labeling compound of the following structure:
- View Dependent Claims (110, 111, 112, 113, 114, 115, 116, 118, 119, 120, 122, 123, 124, 126, 127, 128, 129, 130, 131, 132, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 146, 147, 148, 149, 150, 151, 152, 154, 155, 156, 157, 158, 159, 160, 162, 163, 164, 166, 167, 168)
- - 110. A nucleic acid labeling compound according to claim 109, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 111. A nucleic acid labeling compound according to claim 110, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1.
  - 112. A nucleic acid labeling compound according to claim 110, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1.
  - 113. A nucleic acid labeling compound according to claim 110, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 114. A nucleic acid labeling compound according to claim 110, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 115. A nucleic acid labeling compound according to claim 110, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 116. A nucleic acid labeling compound according to claim 110, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 118. A nucleic acid labeling compound according to claim 117, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      CH═
      
      CH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 119. A nucleic acid labeling compound according to claim 118, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 120. A nucleic acid labeling compound according to claim 118, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 122. A nucleic acid labeling compound according to claim 121, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      CH═
      
      CH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 123. A nucleic acid labeling compound according to claim 122, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 124. A nucleic acid labeling compound according to claim 122, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 126. A nucleic acid labeling compound according to claim 125, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      C(O)NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or a carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 127. A nucleic acid labeling compound according to claim 126, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 128. A nucleic acid labeling compound according to claim 126, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 129. A nucleic acid labeling compound according to claim 126, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 130. A nucleic acid labeling compound according to claim 126, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 131. A nucleic acid labeling compound according to claim 126, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 132. A nucleic acid labeling compound according to claim 126, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      C(O)NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 134. A nucleic acid labeling compound according to claim 133, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 135. A nucleic acid labeling compound according to claim 134, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 136. A nucleic acid labeling compound according to claim 134, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 137. A nucleic acid labeling compound according to claim 134, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 138. A nucleic acid labeling compound according to claim 134, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 139. A nucleic acid labeling compound according to claim 134, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 140. A nucleic acid labeling compound according to claim 134, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 141. A nucleic acid labeling compound according to claim 133, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 2.
  - 142. A nucleic acid labeling compound according to claim 133, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 2.
  - 143. A nucleic acid labeling compound according to claim 134, wherein A is H;
    - Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 144. A nucleic acid labeling compound according to claim 134, wherein A is H₄O₉P₃—
    - ;
      
      Y is H;
      
      Z is H;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 146. A nucleic acid labeling compound according to claim 145, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      C≡
      
      C(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 147. A nucleic acid labeling compound according to claim 146, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 1.
  - 148. A nucleic acid labeling compound according to claim 146, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      C═
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 1.
  - 149. A nucleic acid labeling compound according to claim 146, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 150. A nucleic acid labeling compound according to claim 146, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      C═
      
      CCH₂NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 151. A nucleic acid labeling compound according to claim 146, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 152. A nucleic acid labeling compound according to claim 146, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      C≡
      
      CCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 154. A nucleic acid labeling compound according to claim 153, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      NH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 2 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 155. A nucleic acid labeling compound according to claim 154, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1.
  - 156. A nucleic acid labeling compound according to claim 154, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      , wherein m is 1.
  - 157. A nucleic acid labeling compound according to claim 154, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)4NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 158. A nucleic acid labeling compound according to claim 154, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is biotin; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 159. A nucleic acid labeling compound according to claim 154, wherein A is H;
    - Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 160. A nucleic acid labeling compound according to claim 154, wherein A is H₄O₉P₃—
    - ;
      
      Y is OH;
      
      Z is OH;
      
      L is —
      
      NH(CH₂)₄NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH, wherein m is 1.
  - 162. A nucleic acid labeling compound according to claim 161, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      CH═
      
      CH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 163. A nucleic acid labeling compound according to claim 162, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 164. A nucleic acid labeling compound according to claim 162, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.
  - 166. A nucleic acid labeling compound according to claim 165, wherein A is H or H₄O₉P₃—
    - ;
      
      X is O;
      
      Y is H or OR₉, wherein R₉is H, alkyl or aryl;
      
      Z is H, N₃, F or OR₁₀, wherein R₁₀is H, alkyl or aryl;
      
      L is —
      
      CH═
      
      CH(CH₂)_nNH—
      
      , wherein n is an integer ranging from about 1 to about 10;
      
      Q is biotin or carboxyfluorescein; and
      
      M is —
      
      CO(CH₂)₅NH—
      
      or —
      
      CO(CH₂)₅NHCO(CH₂)₅NH—
      
      , wherein m is 1 or 0.
  - 167. A nucleic acid labeling compound according to claim 166, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is biotin; and
      
      m is 0.
  - 168. A nucleic acid labeling compound according to claim 166, wherein Y is H or OH;
    - Z is H or OH;
      
      L is —
      
      CH═
      
      CHCH₂NH—
      
      ;
      
      Q is 5-carboxyfluorescein; and
      
      m is 0.

117. A nucleic acid labeling compound of the following structure:

121. A nucleic acid labeling compound of the following structure:

125. A nucleic acid labeling compound of the following structure:

133. A nucleic acid labeling compound of the following structure:

145. A nucleic acid labeling compound of the following structure:

153. A nucleic acid labeling compound of the following structure:

161. A nucleic acid labeling compound of the following structure:

165. A nucleic acid labeling compound of the following structure:

169. A nucleic acid labeling compound of the following structure:

170. A nucleic acid labeling compound of the following structure:

171. A nucleic acid labeling compound ofthe following structure:

Specification

Resources

Litigation Campaign Assessment

Current Assignee
Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
Original Assignee
Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
Inventors
Barone, Anthony D., McGall, Glenn

Granted Patent

US 6,965,020 B2
Time in Patent Office

Days
Field of Search
US Class Current

536/23.1
CPC Class Codes

C07H 19/052   Imidazole radicals

C07H 19/12   Triazine radicals

C07H 21/00   Compounds containing two or...

C40B 40/00   Libraries per se, e.g. arra...

Nucleic acid labeling compounds

First Claim

5 Assignments

0 Petitions

Accused Products

Abstract

Citations

171 Claims

Specification

Solutions

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Nucleic acid labeling compounds

First Claim

5 Assignments

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

Citations

171 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links