Claims
- 1. A compound of the structure:
- 2. The compound of claim 1 wherein G2 is a polycyclic moiety having from two to six rings, at least two of said rings being joined to form a conjugated ring system.
- 3. The compound of claim 2 wherein G2 is an intercalator.
- 4. The compound of claim 1 wherein G2 is naphthalene, anthracene, phenanthrene, benzonaphthalene, fluorene, carbazole, pyrido[4,3-b]carbazole, acridine, pyrene, anthraquinone, quinoline, phenylquinoline, xanthene or 2,7-diazaanthracene.
- 5. The compound of claim 1 wherein G1 includes a heteroatom selected from O, S, NH and N-alkyl covalently bound with an alkyl, alkenyl or alkynyl group.
- 6. The compound of claim 1 wherein G3 includes at least one imidazole moiety.
- 7. The compound of claim 1 wherein G3 is an imidazole; a C2-substituted imidazole; an imidazole substituted at a C4 or C5 position with an electrophilic catalyst; a bis-imidazole; a C2-substituted bis-imidazole; a bis-imidazole wherein at least one C4 or C5 position is substituted with an electrophilic catalyst; a bis-imidazole wherein both C4 positions or both C5 positions are substituted with electrophilic catalyst; or a bis-imidazole wherein the linkage between the imidazole rings is substituted with an electrophilic catalyst.
- 8. The compound of claim 7 wherein said electrophilic catalyst comprises a nitrogen functionality that can be protonated.
- 9. The compound of claim 8 wherein said nitrogen functionality is an amine, a nitrogen heterocycle, guanidine or amidine.
- 10. The compound of claim 1 wherein G2 and G3 are connected through a single covalent bond, a bivalent linker or both a single covalent and a bivalent linker.
- 11. The compound of claim 10 wherein G2 and G3 are connected through a single covalent bond.
- 12. The compound of claim 11 wherein G3 includes at least one imidazole moiety covalently bound through a C4 or C5 position.
- 13. The compound of claim 10 wherein said bivalent linker includes an electrophilic catalyst.
- 14. The compound of claim 13 wherein said electrophile comprises a nitrogen functionality that can be protonated.
- 15. The compound of claim 1 wherein G3 includes two imidazole rings linked to said G2 through at least one acyl moiety.
- 16. The compound of claim 10 wherein:
G3 includes at least one imidazole moiety; G2 and G3 are connected through both a single covalent bond and a bivalent linker; said single covalent bond attaches to said imidazole moiety at a C4 or C5 position of said imidazole moiety; and said bivalent linker attaches to said imidazole moiety a C4 or C5 position of said imidazole moiety.
- 17. The compound of claim 1 wherein G1 is connected to G0 at a 2′ sugar position, a heterocyclic base or an internucleoside phosphate linkage of said G0.
- 18. The compound of claim 1 wherein G1 connects to G0 at a 2′ sugar position of said G0.
- 19. A compound of the structure:
- 20. The compound of claim 19 wherein G2 is an intercalator.
- 21. The compound of claim 19 wherein G1″ is alkyl, alkenyl or alkynyl.
- 22. The compound of claim 19 wherein G1″ is alkynyl.
- 23. The compound of claim 19 wherein G1′ is O, S, NH or N-alkyl.
- 24. The compound of claim 19 wherein G1′ is O.
- 25. The compound of claim 19 wherein G3 is a moiety having general acid/base properties.
- 26. The compound of claim 19 wherein G2 includes a polycyclic system.
- 27. The compound of claim 26 wherein said polycyclic system has two to six rings and at least two of said rings are conjugated.
- 28. The compound of claim 19 wherein G2 is naphthalene, anthracene, phenanthrene, benzonaphthalene, fluorene, carbazole, acridine, pyrene, anthraquinone, quinoline, phenylquinoline, xanthene or 2,7-diazaanthracene.
- 29. The compound of claim 19 wherein G3 includes at least one heterocyclic ring.
- 30. The compound of claim 29 wherein said heterocyclic ring includes at least one nitrogen atom.
- 31. The compound of claim 19 wherein G3 includes at least one imidazole moiety.
- 32. The compound of claim 19 wherein G3 is an imidazole moiety.
- 33. The compound of claim 19 wherein G3 is a bis-imidazole moiety.
- 34. The compound of claim 19 wherein Bx is a purine heterocyclic base.
- 35. A compound of the structure:
- 36. The compound of claim 35 wherein G1″ is propargyl.
- 37. The compound of claim 35 wherein G1′ is O, S or NH.
- 38. A chemical compound having one of the structures:
- 39. The compound of claim 38 wherein Sg is a sugar moiety having one of the structures:
- 40. A sequence of linked nucleoside units comprising at least one compound of claim 38 attached to at least one of the nucleoside units.
- 41. A composition for modulating the activity of RNA, comprising at least one compound of claim 1.
- 42. A composition for modulating the activity of RNA, comprising at least one compound of claim 38.
- 43. A composition for modulating the activity of RNA, comprising:
a targeting portion specifically hybridizable with a preselected nucleotide sequence of the RNA; and a portion which is capable of cleaving a phosphodiester bond in said RNA and which comprises a compound of claim 1.
- 44. A composition for modulating the activity of RNA, comprising:
a targeting portion specifically hybridizable with a preselected nucleotide sequence of the RNA; and a portion which is capable of intercalating with and cleaving said RNA and which comprises a compound of claim 1.
- 45. The composition of claim 44, wherein said portion capable of cleaving said RNA is adapted for placement into a minor groove site of a hybrid structure formed from said RNA and said composition.
- 46. A composition for modulating the activity of RNA, comprising:
a targeting portion specifically hybridizable with a preselected nucleotide sequence of the RNA; and a ribofuranosyl nucleotide which bears at its 2′ site a reactive portion capable of intercalating and cleaving RNA.
- 47. A method for modulating the activity of RNA, comprising contacting said RNA with the composition of claim 43.
- 48. A method for modulating the activity of RNA, comprising contacting said RNA with the composition of claim 44.
- 49. A method for modulating the activity of RNA, comprising contacting said RNA with the composition of claim 46.
- 50. A method for modulating the production of a protein by an organism, comprising contacting said organism with the composition of claim 46.
- 51. A method for treating an animal having a disease characterized by undesired production of a protein, comprising contacting the animal with the composition of claim 46.
- 52. A method for detecting the presence or absence of an RNA in a sample suspected of containing RNA, comprising:
contacting the sample with the composition of claim 46; and detecting cleavage of the RNA by the composition.
- 53. Cleaved RNA produced by the method of claim 52.
- 54. A process for preparing a compound having structure:
- 55. The process of claim 54 wherein T3 and T5 together form a 3,5-O-tetraisoproyldisiloxanyl group.
- 56. The process of claim 54 wherein G1′ is O, G1″ is propargyl, and T6 is trifluoromethylsulfonyl.
- 57. The process of claim 54 wherein T7 is TBDMS, G3 is N,N,-dimethyl-imidazole-1-sulfonamidyl and T8 is tributyl.
- 58. The process of claim 54 wherein said contacting steps are performed in the presence of Pd(PPh3)4.
- 59. The compound of claim 1 wherein G3 includes at least two ligands for coordinating with at least one metal ion.
- 60. The compound of claim 1 wherein G3 includes a plurality of ligands for coordinating with at least one of a tetracoordinate, pentacoordinate or hexacoordinate metal ion.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/US93/02057 |
Mar 1993 |
US |
|
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application Ser. No. 942,961 filed Sep. 10, 1992, which is a continuation-in-part of application Ser. No. 846,556, filed Mar. 5, 1992, which is a continuation-in-part of application Ser. No. US91/00243, filed Jan. 11, 1991, which is a continuation-in-part of application Ser. No. 463,358, filed Jan. 11, 1990 and application Ser. No. 566,977, filed Aug. 13, 1990. These applications are assigned to the assignee of this invention. The entire disclosure of each is incorporated herein by reference.
Divisions (1)
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Number |
Date |
Country |
Parent |
08295744 |
Aug 1994 |
US |
Child |
09974326 |
Oct 2001 |
US |
Continuation in Parts (4)
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Number |
Date |
Country |
Parent |
07942961 |
Sep 1992 |
US |
Child |
08295744 |
Aug 1994 |
US |
Parent |
07846556 |
Mar 1992 |
US |
Child |
07942961 |
Sep 1992 |
US |
Parent |
PCT/US91/00243 |
Jan 1991 |
US |
Child |
07846556 |
Mar 1992 |
US |
Parent |
07463358 |
Jan 1990 |
US |
Child |
PCT/US91/00243 |
Jan 1991 |
US |