BASELESS NUCLEOTIDE ANALOGUES AND USES THEREOF

• US 20090155795A1
• Filed: 11/06/2008
• Published: 06/18/2009
• Est. Priority Date: 11/06/2007
• Status: Active Grant

• Current Assignee: Roche Molecular Systems Inc (Roche Holding AG)
• Original Assignee: Osmetech Molecular Diagnostics (Roche Holding AG)
• Inventors: Chunlin, Tao
• Granted Patent: US 7,820,391 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C07F 17/00 Metallocenes
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

A method of detecting a target nucleic acid.

Claims

1. An analog compound having formula (I):

2. A compound according to claim 1, wherein said redox active moiety comprises a metallocene.

3. A compound according to claim 1, wherein said redox active moiety comprises a metallocene derivative.

4. A compound according to claim 2, wherein said metallocene is a ferrocene.

5. A compound according to claim 3, wherein said metallocene derivative is a ferrocene derivative.

6. A compound according to claim 1, wherein at least one of said protection groups P₁ or P₂ is dimethoxytrityl (“

DMT”

).

7. A compound according to claim 1, wherein said backbone spacer X is a C₃ alkyl group.

8. A compound according to claim 1, wherein said solubility moiety has the formula:

9. A compound according to claim 1, wherein said linkers L₁ and L₂ are C₁ alkyl and n is 1 and m is 4.

10. A compound according to claim 1, wherein said backbone spacer is selected from the group consisting of alkyl and substituted alkyl.

11. A compound according to claim 1, wherein said linkers are selected from the group consisting of alkyl and substituted alkyl.

12. A compound according to claim 1, having the formula (II):

13. A compound according to claim 12, wherein R₁ and R₂ are H.

14. A compound according to claim 12, wherein R₁ is H and R₂ is Cl.

15. A compound according to claim 12, wherein R₁ and R₂ are Cl.

16. A compound according to claim 1, having the formula (III)

17. A composition comprising a compound according to any one of claims 1 to 16.

18. A nucleic aids derivative polymer comprising an analogue compound according to claim 1 having formula (IV):

19. A nucleic acid derivative comprising a compound according to claim 1, wherein at least one of P₁ and P₂ is a nucleoside containing group.

20. A nucleic acid derivative according to claim 19, wherein both P₁ and P₂ are nucleoside containing groups.

21. A method of making a nucleic acid according to any one of claims 16-20, wherein said method comprises:

a) coupling a nucleotide with a resin;

b) deprotecting said compound; and

c) coupling said nucleotide with said compound;

22. A method of detecting a target nucleic acid comprising:

a) providing a substrate comprising;

i) an electrode;

ii) a self-assembled monolayer (SAM) on said electrode; and

iii) a capture probe disposed on said electrode, wherein said capture probe binds to said target nucleic acid;

b) forming a complex comprising said capture probe, said target nucleic acid, and a label probe comprising the nucleic acid derivative according to anyone of claims 16-20; and

c) detecting electron transfer from a redox active moiety of said label probe to said conductive surface of said electrode to detect said target nucleic acid.

23. A kit comprising one or more members from the group consisting of a compound according to claim 1 and a nucleic acid derivative according to claim 18.

24. A compound of formula W330.

25. Compositions comprising W330 incorporated as a linker.