Compositions and methods using platinum compounds for nucleic acid labeling
First Claim
1. A composition comprising the formula:
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wherein;
R1-R5 may be the same or different and are independently selected from the group consisting of H, alkyl (1 to 10 carbon atoms), benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R6, —
(C═
O)OR6, or —
OCH2(C═
O)R6 and a salt, wherein R6 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 may be the same or different and at least one of X1 or X2 is a leaving group; and
linker is a moiety joining a nitrogen to a detectable marker, D.
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Accused Products
Abstract
The invention relates to novel platinum-based compounds for labeling biomolecules. Platinum based labeling compounds according to the invention irreversibly attach to a target biomolecule via coordination of a platinum (II) metal center with N or S atoms on the target biomolecule. The invention relates to the novel compounds themselves, methods of making the platinum-based labeling compounds, probes labeled with such compounds, methods of making such labeled probes, and kits comprising the novel platinum-based labeling compounds and/or probes labeled with them. The invention also relates to methods of using probes labeled with platinum-based labeling compounds of the invention, particularly array and microarray hybridization methods.
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Citations
104 Claims
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1. A composition comprising the formula:
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wherein; R1-R5 may be the same or different and are independently selected from the group consisting of H, alkyl (1 to 10 carbon atoms), benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R6, —
(C═
O)OR6, or —
OCH2(C═
O)R6 and a salt, wherein R6 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 may be the same or different and at least one of X1 or X2 is a leaving group; and
linker is a moiety joining a nitrogen to a detectable marker, D. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
and A, B, D, and B are the same or different and are selected from the group consisting of CH, N, O and S.
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4. The composition of claim 1 wherein the detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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5. A nucleic acid comprising a composition of claim 1.
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6. The nucleic acid of claim 5 wherein said composition forms a non-covalent adduct with said nucleic acid.
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7. A probe comprising a composition of claim 1.
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8. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 1 with said nucleic acid.
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9. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 6 and detecting signal from said detectable marker.
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10. A composition comprising the formula:
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wherein; R1-R5 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R6, —
(C═
O)OR6, or —
OCH2(C═
O)R6 and a salt, wherein R6 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 may be the same or different and at least one of X1 and X2 is a leaving group; and
linker is a moiety joining a nitrogen to a detectable marker, D. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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13. The composition of claim 10 wherein the detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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14. A nucleic acid comprising a composition of claim 10.
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15. The nucleic acid of claim 14 wherein said composition fonus a non-covalent adduct with said nucleic acid.
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16. A probe comprising a composition of claim 10.
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17. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 10 with said nucleic acid.
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18. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 15 and detecting signal from said detectable marker.
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19. A composition comprising the formula:
-
wherein Y is selected from the group consisting of O, S, and C;
R1 is selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R2, —
(C═
O)OR2, —
OCH2(C═
O)R2, and a salt, wherein R2 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 are the same or different and at least one of X1 or X2 is a leaving group;
linker is a moiety joining a nitrogen to a detectable marker, D, and u and v are the same or different and are an integer from 1 to 10. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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22. The composition of claim 19 wherein said detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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23. A nucleic acid comprising a composition of claim 19.
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24. The nucleic acid of claim 23 wherein said composition fonns a non-covalent adduct with said nucleic acid.
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25. A probe comprising a composition of claim 19.
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26. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 19 with said nucleic acid.
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27. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 25 and detecting signal from said detectable marker.
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28. A composition comprising the formula:
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wherein; —
Y is selected from the group consisting of O, S, and C;
R1-R3 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R4, —
(C═
O)OR4, or —
OCH2(C═
O)R4 and a salt, wherein R4 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 are the same or different and at least one of X1 or X2 is a leaving group; and
linker is a moiety joining a nitrogen to a detectable marker, D. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36)
and A, B, D, and E are the same or different and are selected from the group consisting of OH, N, O and S.
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31. The composition of claim 28 wherein said detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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32. A nucleic acid comprising a composition of claim 28.
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33. The nucleic acid of claim 32 wherein said composition forms a non-covalent adduct with said nucleic acid.
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34. A probe comprising a composition of claim 28.
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35. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 28 with said nucleic acid.
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36. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 34 and detecting signal from said detectable marker.
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37. A composition comprising the formula:
-
wherein; Y is selected from the group consisting of O, S, and C;
R1-R3 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R4, —
(C═
O)OR4, or —
OCH2(C═
O)R4 and a salt, wherein R4 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 are the same or different and at least one of X1 or X2 is a leaving group; and
linker is a moiety joining a nitrogen to a detectable marker, D. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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40. The composition of claim 37 wherein said detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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41. A nucleic acid comprising a composition of claim 37.
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42. The nucleic acid of claim 41 wherein said composition forms a non-covalent adduct with said nucleic acid.
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43. A probe comprising a composition of claim 37.
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44. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 37 with said nucleic acid.
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45. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 43 and detecting signal from said detectable marker.
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46. A composition comprising the formula
wherein Z is selected from the group consisting of (CH2)n, and (CH2)nO(CH2)m, wherein m and n are integers from 2 to 8, inclusive; -
R1 is selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R2, —
(C═
O)OR2, or —
OCH2(C═
O)R2 and a salt, wherein R2 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X1 and X2 are the same or different and at least one of X1 and X2 is a leaving group; and
linker is a moiety joining a nitrogen to a detectable marker, D. - View Dependent Claims (47, 48, 49, 50, 51, 52, 53, 54)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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49. The composition of claim 46 wherein said detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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50. A nucleic acid comprising a composition of claim 46.
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51. The nucleic acid of claim 50 wherein said composition forms a non-covalent adduct with said nucleic acid.
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52. A probe comprising a composition of claim 46.
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53. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 46 with said nucleic acid.
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54. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 52 and detecting signal from said detectable marker.
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55. A composition comprising the formula
wherein Z is selected from the group consisting of (CH2)n, and (CH2)nO(CH2)m, wherein m and n are integers from 2 to 8, inclusive; -
R1 and R2 may be the same or different and are selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R3, —
(C═
O)OR3, or —
OCH2(C═
O)R3 and a salt, wherein R3 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X is a leaving group; and
linker is a moiety joining a detectable marker, D to the platinum ion. - View Dependent Claims (56, 57, 58, 59, 60, 61, 62, 63)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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58. The composition of claim 55 wherein said detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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59. A nucleic acid comprising a composition of claim 55.
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60. The nucleic acid of claim 59 wherein said composition forms a non-covalent adduct with said nucleic acid.
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61. A probe comprising a composition of claim 55.
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62. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 55 with said nucleic acid.
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63. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 61 and detecting signal from said detectable marker.
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64. A composition comprising the formula:
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wherein; R1-R6 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R7, —
(C═
O)OR7, or —
OCH2(C═
O)R7 and a salt, wherein R7 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X is a leaving group; and
linker is a moiety joining a detectable marker, D to the platinum ion. - View Dependent Claims (65, 66, 67, 68, 69, 70, 71, 72)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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67. The composition of claim 64 wherein the detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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68. A nucleic acid comprising a composition of claim 64.
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69. The nucleic acid of claim 68 wherein said composition forms a non-covalent adduct with said nucleic acid.
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70. A probe comprising a composition of claim 64.
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71. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 67 with said nucleic acid.
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72. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 70 and detecting signal from said detectable marker.
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73. A composition comprising the formula
wherein R1-R6 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O— - R7, —
(C═
O)OR7, or —
OCH2(C═
O)R7 and a salt, wherein R7 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X is a leaving group; and
linker is a moiety joining a detectable marker, D, to the platinum ion. - View Dependent Claims (74, 75, 76, 77, 78, 79, 80, 81)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
- R7, —
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76. The composition of claim 73 wherein the detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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77. A nucleic acid comprising a composition of claim 73.
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78. The nucleic acid of claim 77 wherein said composition forms a non-covalent adduct with said nucleic acid.
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79. A probe comprising a composition of claim 73.
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80. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 73 with said nucleic acid.
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81. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 79 and detecting signal from said detectable marker.
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82. A composition comprising the formula:
-
wherein Y is selected from the group consisting of O, S, and C;
R1-R4 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R5, —
(C═
O)OR5, or —
OCH2(C═
O)R5 and a salt, wherein R5 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X is a leaving group; and
linker is a moiety joining a detectable marker, D, to the platinum ion. - View Dependent Claims (83, 84, 85, 86, 87, 88, 89, 90)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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85. The composition of claim 82 herein the detectable marker, D, is selected from the group consisting of a fluorophore, a chromophore, a radiolabel, an enzyme and an affinity tag.
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86. nucleic acid comprising a composition of claim 82.
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87. The nucleic acid of claim 86 wherein said composition forms a non-covalent adduct with said nucleic acid.
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88. A probe comprising a composition of claim 82.
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89. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 82 with said nucleic acid.
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90. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 88 and detecting signal from said detectable marker.
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91. A composition comprising the formula:
-
wherein Y is selected from the group consisting of O, S, and C;
R1-R4 may be the same or different and are independently selected from the group consisting of H, methyl, benzyl, sulfonate, phosphonate, NO2, CF3, halogen, O—
R5, —
(C═
O)OR5, or —
OCH2(C═
O)R5 and a salt, wherein R5 is a straight or branched, saturated or unsaturated, substituted or unsubstituted alkyl having 1-10 carbons;
X is a leaving group; and
linker is a moiety joining a detectable marker, D, to the platinum ion. - View Dependent Claims (92, 93, 94, 95, 96, 97, 98, 99)
and A, B, D, and E are the same or different and are selected from the group consisting of CH, N, O and S.
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94. The composition of claim 91 wherein the detectable marker, D, is selected from the group consisting of a fluorophore, a chrornophore, a radiolabel, an enzyme and an affinity tag.
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95. A nucleic acid comprising a composition of claim 91.
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96. The nucleic acid of claim 95 wherein said composition forms a non-covalent adduct with said nucleic acid.
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97. A probe comprising a composition of claim 91.
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98. A method of labeling a nucleic acid, said method comprising the step of contacting a composition of claim 91 with said nucleic acid.
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99. A method of probing a nucleic acid array, said method comprising the steps of contacting said array with a probe of claim 97 and detecting signal from said detectable marker.
- 100. A method of making a platinum labeling compound that comprises a stabilizing bridge, the method comprising the step of contacting potassium tetrachloroplatinate (II) with a cycloaliphatic diamine labeled with a detectable marker, wherein said contacting results in a cis-platinum dichloride labeling compound.
Specification