Nucleic acid labeling compounds

• US 7,491,818 B2
• Filed: 01/18/2005
• Issued: 02/17/2009
• Est. Priority Date: 07/31/1998
• Status: Expired due to Fees

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: McGall, Glenn, Barone, Anthony D.
• Primary Examiner(s): Lewis; Patrick T
• Application Number:
  US11/037,065
• Publication Number:
  US 20050164268A1
• Time in Patent Office: 1,491 Days
• Field of Search: None
• US Class Current: 536/26.8
• 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 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• 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

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 comprising the formula:

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 R₉ is H, alkyl or aryl;

Z is H, N₃, F or OR₁₀, wherein R₁₀ is 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.

3. A nucleic acid labeling compound according to claim 2, 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.

4. A nucleic acid labeling compound according to claim 2, 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.

5. A nucleic acid labeling compound according to claim 2, 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.

6. A nucleic acid labeling compound according to claim 2, 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.

7. A nucleic acid labeling compound according to claim 2, 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.

8. A nucleic acid labeling compound according to claim 2, 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.

17. A nucleic acid labeling compound according to claim 1, wherein the compound has the formula:

20. A nucleic acid labeling compound according to claim 1, wherein the compound has the formula:

23. A nucleic acid labeling compound according to claim 1, wherein the compound has the formula:

9. A nucleic acid labeling compound comprising the formula:

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 R₉, is H, alkyl or aryl;

Z is H, N₃, F or OR₁₀, wherein R₁₀ is 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.

11. A nucleic acid labeling compound according to claim 10, wherein Y is H or OH;

Z is H or OH;

L is —

CH═

CHCH₂NH—

;

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 —

CH═

CHCH₂NH—

;

Q is 5-carboxyfluorescein; and

m is 0.

18. A nucleic acid labeling compound according to claim 9, wherein the compound has the formula:

21. A nucleic acid labeling compound according to claim 9, wherein the compound has the formula:

24. A nucleic acid labeling compound according to claim 9, wherein the compound has the formula:

13. A nucleic acid labeling compound comprising the formula:

14. A nucleic acid labeling compound according to claim 13, wherein A is H or H₄O₉P₃—

;

X is O;

Y is H or OR₉, wherein R₉ is H, alkyl or aryl;

Z is H, N₃, F or OR₁₀, wherein R₁₀ is 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.

15. A nucleic acid labeling compound according to claim 14, wherein Y is H or OH;

Z is H or OH;

L is —

CH═

CHCH₂NH—

;

Q is biotin; and

m is 0.

16. A nucleic acid labeling compound according to claim 14, wherein Y is H or OH;

Z is H or OH;

L is —

CH═

CHCH₂NH—

;

Q is 5-carboxyfluorescein; and

m is 0.

19. A nucleic acid labeling compound according to claim 13, wherein the compound has the formula:

22. A nucleic acid labeling compound according to claim 13, wherein the compound has the formula:

25. A nucleic acid labeling compound according to claim 13, wherein the compound has the formula: