STABILIZED NUCLEIC ACID DARK QUENCHER-FLUOROPHORE PROBES

• US 20110282041A1
• Filed: 07/28/2011
• Published: 11/17/2011
• Est. Priority Date: 04/01/2008
• Status: Active Grant

• Current Assignee: HSB Corporate Trust Company (UK) Limited
• Original Assignee: Biosearch Technologies Incorporated
• Inventors: Lyttle, Matt, Cook, Ronald M.
• Granted Patent: US 8,674,094 B2
• Time in Patent Office: Days
• US Class Current: 534/727
• CPC Class Codes: C07D 219/04 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C09B 31/02 Disazo dyes
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes

Abstract

The present invention provides a new class of solids supports for synthesis of modified oligomers of nucleic acids, and nucleic acid probes that have a format expediently synthesized on the new supports. Exemplary solid supports include at least one quencher bound through a linker to the solid support. Various exemplary embodiments include a moiety that stabilizes a duplex, triplex or higher order aggregation (e.g., hybridization) of nucleic acids of which the oligomer of the invention is a component. Other components of the solid support include moieties that stabilize aggregations of nucleic acids, e.g., intercalators, minor groove binding moieties, bases modified with a stabilizing moiety (e.g., alkynyl moieties, and fluoroalkyl moieties), and conformational stabilizing moieties, such as those described in commonly owned U.S. Patent Application Publication No. 2007/0059752.

Claims

1. A monomeric nucleic acid having the formula:

2. The monomeric nucleic acid according to claim 1, wherein said linker is a member selected from a single covalent bond, substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl.

3. The monomeric nucleic acid according to claim 1, wherein R^d is a nucleic acid protecting group.

4. The monomeric nucleic acid according to claim 3, wherein said nucleic acid protecting group is DMT.

5. The monomeric nucleic acid according to claim 1, wherein R^c is —

OPN(i-Pr)₂(OCNE).

6. The monomeric nucleic acid according to claim 1, wherein said base is a member selected from:

7. The monomeric nucleic acid according to claim 1, wherein Q-L⁴ has the formula:

8. The monomeric nucleic acid according to claim 1, wherein said quencher has a structure according to Formula (II)

9. The monomeric nucleic acid according to claim 8, wherein said quencher has a structure according to Formula (III):

10. The monomeric nucleic acid according to claim 8, wherein a member selected from R¹, R² and R³ includes a structure according to Formula IV:

11. The monomeric nucleic acid according to claim 8, wherein said quencher has a structure according to Formula V:

12. The monomeric nucleic acid according to claim 11, wherein said quencher has a structure according to Formula VI:

13. The monomeric nucleic acid according to claim 8, wherein said quencher has a structure which is a member selected from:

14. The monomeric nucleic acid according to claim 1, having the formula:

15. The monomeric nucleic acid according to claim 1, having the formula:

16. A nucleic acid oligomer, wherein said nucleic acid oligomer is prepared using a monomeric nucleic acid according to claim 1.

17. The nucleic acid oligomer according to claim 16, wherein said nucleic acid oligomer is a probe.

18. The nucleic acid oligomer according to claim 17, wherein said probe is selected from molecular beacons, scorpion probes, sunrise probes, conformationally assisted probes, light up probes, invader detection probes, and taqman probes.