Divalent nucleobase compounds and uses therefor

Patent metadata

Field	Value
Publication number	US-11236130-B2
Application number	US-201916445427-A
Country	US
Kind code	B2
Filing date	Jun 19, 2019
Priority date	Apr 11, 2013
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

Abstract

Described herein are novel divalent nucleobases that each bind two nucleic acid strands, matched or mismatched when incorporated into a nucleic acid or nucleic acid analog backbone (a genetic recognition reagent, or genetic recognition reagent). In one embodiment, the genetic recognition reagent is a peptide nucleic acid (PNA) or gamma PNA (γPNA) oligomer. Uses of the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.

First claim

We claim:

1. A compound comprising a moiety of the formula:

attached to a nucleic acid analogue, wherein each R 1 is independently a protecting group or H, and X is CH or N.

2. The compound of claim 1 , wherein the nucleic acid analogue is a peptide nucleic acid (PNA), phosphorothioate, locked nucleic acid, unlocked nucleic acid, 2′O-methyl-substituted RNA, morpholino nucleic acid, threose nucleic acid, or glycol nucleic acid, or any combination thereof.

3. The compound of claim 1 , wherein the nucleic acid analogue is a peptide nucleic acid (PNA).

4. The compound of claim 3 , wherein the peptide nucleic acid comprises a residue of the formula:

5. The compound of claim 3 , wherein the peptide nucleic acid (PNA) comprises 3-8 PNA subunits.

6. The compound of claim 5 , wherein a series of nucleobases in the peptide nucleic acid (PNA) is complementary to a sequence of nucleobases in a nucleic acid sequence associated with a genetic disease.

7. A method comprising contacting a nucleic acid with a compound, wherein the compound comprises a moiety of the formula:

attached to a nucleic acid analogue wherein each R 1 is independently a protecting group or H, and X is CH or N.

8. The method of claim 7 , wherein the compound further comprises a fluorochrome.

9. The method of claim 7 , wherein the compound is bound to a solid substrate in an array.

10. The method of claim 7 , wherein the nucleic acid is a marker of genetic disease.

11. The method of claim 7 , wherein the nucleic acid is derived from a bacterial, viral, or fungal infection.

12. The method of claim 7 , wherein the contacting occurs inside a human.

13. The method of claim 7 , wherein the nucleic acid analogue is a peptide nucleic acid (PNA), phosphorothioate, locked nucleic acid, unlocked nucleic acid, 2′O-methyl-substituted RNA, morpholino nucleic acid, threose nucleic acid, or glycol nucleic acid, or any combination thereof.

14. The method of claim 13 , wherein the nucleic acid analogue is a peptide nucleic acid (PNA).

15. A method of treating a condition, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound, wherein the compound comprises a moiety of the formula:

attached to a nucleic acid analogue, wherein each R 1 is independently a protecting group or H, and X is CH or N.

16. The method of claim 15 , wherein the nucleic acid analogue is a peptide nucleic acid (PNA) that has a series of nucleobases complementary to a sequence of nucleobases in a nucleic acid derived from a bacterial, viral, or fungal infection.

17. The method of claim 15 , wherein the nucleic acid analogue is a peptide nucleic acid (PNA) that has a series of nucleobases complementary to a sequence of nucleobases in a nucleic acid sequence associated with a genetic disease.

18. The method of claim 17 , wherein the nucleic acid sequence is DNA.

19. The method of claim 17 , wherein the nucleic acid sequence is RNA.

20. The method of claim 17 , wherein the genetic disease is cancer.

Assignees

• Univ Carnegie Mellon

Inventors

• Ly Danith H
• Gopalsamy Suresh Kumar
• Manna Arunava

Classifications

• C07H21/04 Primary

  with deoxyribosyl as saccharide radical · CPC title

• C07D251/16

  to only one ring carbon atom · CPC title

• C07D475/08

  with a nitrogen atom directly attached in position 2 · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07H1/06

  Separation; Purification · CPC title