Propargyl substituted nucleoside compounds and methods

• US 20050214843A1
• Filed: 04/12/2005
• Published: 09/29/2005
• Est. Priority Date: 12/23/2003
• Status: Abandoned Application

• Current Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Jeon, Geun-sook, Khan, Shaheer H., Rosenblum, Barnett B.
• Application Number:
  US11/104,130
• Publication Number:
  US 20050214843A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical

Abstract

The present teachings relate to nucleobase, nucleoside and nucleotide compounds, methods of synthesis, and uses thereof. The present teachings provide compounds, such as nucleobase, nucleoside and/or nucleotide compounds including a propargyl linker, and methods for making or using such compounds.

Claims

1-23. -23. (canceled)

24. A labeled nucleoside comprising a nucleobase disposed between a sugar or a sugar analog and a propargylic moiety, wherein the nucleobase is selected from a pyrimidine base or a pyrimidine base analog, the propargylic moiety is covalently attached to the nucleobase at the C-5 position of the nucleobase, the sugar or sugar analog is covalently attached to the nucleobase at the N−

1 position of the nucleobase, and wherein the propargylic moiety comprises

(i) a propargyl group covalently attached by its methylene carbon to the nucleobase,

(ii) a detectable label, and

(iii) a linker covalently linking the acetylene carbon of the propargyl group to the detectable label.

25. The nucleoside of claim 24 wherein the nucleobase comprises a pyrimidine base.

26. The nucleoside of claim 24 wherein the pyrimidine base is uridine.

27. The nucleoside of claim 24 wherein the sugar comprises ribose, 2′

-deoxyribose or 2′

,3′

-dideoxyribose.

28. The nucleoside of claim 27 wherein the sugar is 2′

,3′

-dideoxyribose.

29. The nucleoside of claim 24 wherein the sugar or sugar analog comprises a compound of the structure:

30. The nucleoside of claim 24 wherein the linker comprises from 1-50 atoms selected from C, H, N, O, S, P and Si.

31. The nucleoside of claim 24 wherein the linker comprises at least one anionic moiety.

32. The nucleoside of claim 24 wherein the linker comprises at least one cationic moiety.

33. The nucleoside of claim 24 wherein the linker comprises at least one amide linkage.

34. The nucleoside of claim 33 wherein the linker comprises at least one diradical selected from

35. The nucleoside of claim 33 wherein the linker comprises at least one diradical selected from

36. The nucleoside of claim 35 wherein Z is unsubstituted amine.

37. The nucleoside of claim 35 wherein Z is substituted amine.

38. The nucleoside of claim 24 wherein the detectable label comprises at least one of a fluorescent dye, an energy transfer dye, a quencher or biotin.

39. The nucleoside of claim 24 wherein the detectable label comprises a rhodamine dye, a fluorescein dye, a rhodol dye, an energy transfer dye, a cyanine dye, a phthalocyanine and a squaraine.

40. The nucleoside of claim 24 wherein the detectable label comprises a fluorescein dye, a rhodamine dye or an energy transfer dye.

41. The nucleoside of claim 24 wherein the detectable label comprises an energy transfer dye comprising a donor dye covalently attached to an acceptor dye, wherein either the donor dye or the acceptor dye is covalently attached to the linker, and the acceptor dye is capable of absorbing the light emitted by the donor dye.

42. The nucleoside of claim 41 wherein the donor dye is covalently attached to the linker.

43. The nucleoside of claim 41 wherein the donor dye comprises a fluorescein dye or a rhodamine dye.

44. The nucleoside of claim 43 wherein the acceptor dye comprises one of a rhodamine dye, a fluorescein dye, a cyanine dye or a non-fluorescent quencher.

45. The nucleoside of claim 44 wherein the donor dye is covalently linked to the acceptor dye through a linker-moiety.

46. The nucleoside of claim 41 wherein the donor dye comprises a fluorescein or a rhodamine dye and the acceptor dye is a non-fluorescent quencher.

47-69. -69. (canceled)

70. A nucleoside comprising a nucleobase disposed between a sugar or a sugar analog and a propargylic moiety, wherein the nucleobase is selected from a pyrimidine base or a pyrimidine base analog, the propargylic moiety is covalently attached to the nucleobase at the C-5 position of the nucleobase, the sugar or sugar analog is covalently attached to the nucleobase at the N−

1 position of the nucleobase, and wherein the propargylic moiety comprises a propargyl group covalently attached to the nucleobase at the methylene carbon of the propargyl group.

71. The nucleoside of claim 70 wherein the nucleobase comprises a pyrimidine base.

72. The nucleoside of claim 70 wherein the pyrimidine base is uridine.

73. The nucleoside of claim 70 wherein the sugar comprises ribose, 2′

-deoxyribose or 2′

,3′

-dideoxyribose.

74. The nucleoside of claim 70 wherein the sugar is 2′

,3′

-dideoxyribose.

75. The nucleoside of claim 70 wherein the sugar or sugar analog comprises a compound of the structure:

76. The nucleoside of claim 70 wherein the linker comprises from 1-50 atoms selected from C, H, N, O, S, P and Si.

77. The nucleoside of claim 70 wherein the linker comprises at least one anionic moiety.

78. The nucleoside of claim 70 wherein the linker comprises at least one cationic moiety.

79. The nucleoside of claim 70 wherein the linker comprises at least one amide linkage.

80. The nucleoside of claim 79 wherein the linker comprises at least one diradical selected from

81. The nucleoside of claim 79 wherein the linker comprises at least one diradical selected from

82. The nucleoside of claim 81 wherein Z is unsubstituted amine.

83. The nucleoside of claim 81 wherein Z is substituted amine.

84-102. -102. (canceled)

103. A method for making a thymidine analog comprising:

contacting a protected or unprotected 5-halomethyl uridine nucleotide with a copper acetylide to form an adduct comprising a 5-propargyl uridine.

104. The method of claim 103 wherein the copper acetylide comprises a mixture comprising a copper reagent, a base and an alkyne.

105. (canceled)