Conjugates and compositions for cellular delivery
View Patent ↗This invention features conjugates, compositions, methods of synthesis, and applications thereof, including folate derived conjugates of nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids and antisense nucleic acid molecules.
1. A compound having the formula II:
wherein each R 3 , R 4 , R 5 , R 6 and R 7 is independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, or a protecting group, each “n” is independently an integer from 0 to about 200, R 12 is a straight or branched chain alkyl, substituted alkyl, aryl, or substituted aryl, and R 2 is a phosphorus containing group, a nucleoside, a nucleotide, a small molecule, a nucleic acid, or a solid support comprising a linker.
2. The compound of claim 1 , wherein R 2 is a phosphorus containing group.
3. The compound of claim 1 , wherein R 2 is a nucleoside.
4. The compound of claim 1 , wherein R 2 is a nucleotide.
5. The compound of claim 1 , wherein R 2 is a small molecule.
6. The compound of claim 1 , wherein R 2 is a nucleic acid.
7. The compound of claim 1 , wherein R 2 is a solid support comprising a linker.
8. The compound of claim 3 , wherein said nucleoside is a nucleoside with anticancer activity.
9. The compound of claim 3 , wherein said nucleoside is a nucleoside with antiviral activity.
10. The compound of claim 3 , wherein said nucleoside is fludarabine.
11. The compound of claim 3 , wherein said nucleoside is lamivudine (3TC).
12. The compound of claim 3 , wherein said nucleoside is 5-fluro uridine.
13. The compound of claim 3 , wherein said nucleoside is AZT.
14. The compound of claim 3 , wherein said nucleoside is ara-adenosine or ara-adenosine monophosphate.
15. The compound of claim 3 , wherein said nucleoside is a dideoxy nucleoside analog.
16. The compound of claim 3 , wherein said nucleoside is carbodeoxyguanosine.
17. The compound of claim 3 , wherein said nucleoside is ribavirin.
18. The compound of claim 3 , wherein said nucleoside is fialuridine.
19. The compound of claim 3 , wherein said nucleoside is lobucavir.
20. The compound of claim 3 , wherein said nucleoside is a pyrophosphate nucleoside analog.
21. The compound of claim 3 , wherein said nucleoside is an acyclic nucleoside analog.
22. The compound of claim 3 , wherein said nucleoside is acyclovir.
23. The compound of claim 3 , wherein said nucleoside is gangciclovir.
24. The compound of claim 3 , wherein said nucleoside is penciclovir.
25. The compound of claim 3 , wherein said nucleoside is famciclovir.
26. The compound of claim 3 , wherein said nucleoside is an L-nucleoside analog.
27. The compound of claim 3 , wherein said nucleoside is FTC.
28. The compound of claim 3 , wherein said nucleoside is L-FMAU.
29. The compound of claim 3 , wherein said nucleoside is L-ddC or L-FddC.
30. The compound of claim 3 , wherein said nucleoside is L-d4C or L-Fd4C.
31. The compound of claim 3 , wherein said nucleoside is an L-dideoxypurine nucleoside analog.
32. The compound of claim 3 , wherein said nucleoside is cytallene.
33. The compound of claim 3 , wherein said nucleoside is bis-POM PMEA (GS-840).
34. The compound of claim 3 , wherein said nucleoside is BMS-200,475.
35. The compound of claim 1 , wherein R 4 is tert-butyl, Fm (fluorenyl-methoxy), or allyl.
36. The compound of claim 1 , wherein R 6 is TFA (trifluoracetyl).
37. The compound of claim 1 , wherein R 3 , R 5 and R 7 are hydrogen.
38. The compound of claim 1 , wherein R 7 is isobutyryl.
39. The compound of claim 1 , wherein R 7 is dimethylformamide.
40. The compound of claim 1 , wherein R 7 is hydrogen.
41. The compound of claim 1 , wherein R 12 is methyl.
42. The compound of claim 1 , wherein R 12 is ethyl.
43. The compound of claim 6 , wherein said nucleic acid is an enzymatic nucleic acid.
44. The compound of claim 43 , wherein said enzymatic nucleic acid is a hammerhead.
45. The compound of claim 43 , wherein said enzymatic nucleic acid is an Inozyme.
46. The compound of claim 43 , wherein said enzymatic nucleic acid is a DNAzyme.
47. The compound of claim 43 , wherein said enzymatic nucleic acid is a cleaver.
48. The compound of claim 43 , wherein said enzymatic nucleic acid is a Zinzyme.
49. The compound of claim 43 , wherein said enzymatic nucleic acid is an Amberzyme.
50. The compound of claim 43 , wherein said enzymatic nucleic acid is an allozyme.
51. The compound of claim 6 , wherein said nucleic acid is an antisense nucleic acid.
52. The compound of claim 6 , wherein said nucleic acid is a 2-5A nucleic acid chimera.
53. The compound of claim 6 , wherein said nucleic acid is a decoy nucleic acid.
54. The compound of claim 4 , wherein said nucleotide is a nucleotide with anticancer activity.
55. The compound of claim 4 , wherein said nucleotide is a nucleotide with antiviral activity.
56. The compound of claim 7 , wherein said solid support comprising a linker of Formula XVII:
wherein SS is a solid support, and each “n” is independently an integer from 1 to 200.
57. The compound of claim 56 , wherein said solid support is controlled pore glass (CPG).
58. The compound of claim 56 , wherein said solid support is polystyrene.
59. The compound of claim 7 , wherein said compound is used in the synthesis of a nucleic acid.
60. A pharmaceutical composition comprising the compound of claim 1 in a pharmaceutically acceptable carrier.
61. A kit for detecting the presence of a nucleic acid in a sample, comprising the compound of claim 6 .
62. A kit for detecting the presence of a target molecule in a sample, comprising the compound of claim 6 .
63. A kit for detecting the presence of a nucleic acid in a cancer cell, comprising the compound of any of claim 50 .
64. A kit for detecting the presence of a nucleic acid in a virus infected cell, comprising the compound of claim 50 .
65. The compound of claim 1 , wherein said compound contains a modified phosphate.
66. The compound of claim 1 , wherein said phosphorus containing group is a phosphoramidite, phosphodiester, phosphoramidate, phosphorothioate, phosphorodithioate, alkylphosphonate, arylphosphonate, monophosphate, diphosphate, triphosphate, or pyrophosphate.
67. The compound of claim 3 , wherein said nucleoside is carbovir or abacavir.
68. The compound of claim 1 , wherein R 12 is an alkylhydroxyl.
69. The compound of claim 68 , wherein said alkylhydroxyl is —(CH 2 ) n OH.
70. The compound of claim 69 , wherein said n is an integer from 1–10.
71. The kit of claim 61 , wherein said sample is from a cancer cell.
72. The kit of claim 61 , wherein said sample is from a virus infected cell.
73. The kit of claim 62 , wherein said sample is from a cancer cell.
74. The kit of claim 62 , wherein said sample is from a virus infected cell.