Nucleic acid labeling compounds

• US 20030180757A1
• Filed: 12/05/2002
• Published: 09/25/2003
• Est. Priority Date: 01/23/1996
• Status: Active Grant

• 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 6,864,059 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/052 Imidazole radicals
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/12 Triazine radicals
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 7/00 Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
• CPC Class Codes: C07H 7/06 Heterocyclic radicals
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures

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.

Claims

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

2. A nucleic acid labeling compound according to claim 1 wherein L is —

CH═

CH—

C(O)—

NH—

CH₂—

CH₂—

NH—

C(O)—

.

3. A nucleic acid labeling compound according to claim 1 wherein A is a triphosphate group with apporpriate counterions, said counterions selected from the group consisting of H+, Na+, Li+, K+, and NH₄+.

4. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 1 with a nucleic acid.

5. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 4 bound to a complementary probe.

6. The hybridization product according to claim 5, wherein the probe is attached to a glass chip.

7. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 6 bound to a complementary probe.

8. The hybridization product according to claim 7, wherein the probe is attached to a glass chip.

9. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 1 to a nucleic acid.

10. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 4 with a probe.

11. A method according to claim 10, wherein the probe is attached to a glass chip.

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

13. A nucleic acid labeling compound according to claim 12 wherein A is a triphosphate group with apporpriate counterions, said counterions selected from the group consisting of H+, Na+, Li+, K+, and NH₄+.

14. A nucleic acid labeling compound according to claim 12 wherein L is —

CH═

CH—

C(O)—

NH—

CH₂—

CH₂—

NH—

C(O)—

.

15. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 12 with a nucleic acid.

16. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 15 bound to a complementary probe.

17. The hybridization product according to claim 16, wherein the probe is attached to a glass chip.

18. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 17 bound to a complementary probe.

19. The hybridization product according to claim 18, wherein the probe is attached to a glass chip.

20. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 12 to a nucleic acid.

21. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 15 with a probe.

22. A method according to claim 21, wherein the probe is attached to a glass chip.

24. A nucleic acid labeling compound according to claim 12 wherein A is a triphosphate group with apporpriate counterions, said counterions selected from the group consisting of H+, Na+, Li+, K+, and NH₄+.

23. A nucleic acid labeling compound having the structure

25. A nucleic acid labeling compound according to claim 23 wherein L is —

C(O)(CH2)₅NH—

.

26. A nucleic acid derivative produced by coupling a nucleic acid labeling compound according to claim 23 with a nucleic acid.

27. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 26 bound to a complementary probe.

28. The hybridization product according to claim 27, wherein the probe is attached to a glass chip.

29. A hybridization product, wherein the hybridization product comprises the nucleic acid derivative according to claim 25 bound to a complementary probe.

30. The hybridization product according to claim 29, wherein the probe is attached to a glass chip.

31. A method of synthesizing a labeled nucleic acid comprising attaching a nucleic acid labeling compound according to claim 23 to a nucleic acid.

32. A method of detecting a nucleic acid comprising incubating a nucleic acid derivative according to claim 26 with a probe.

33. A method according to claim 32, wherein the probe is attached to a glass chip.