Multimolecular devices and drug delivery systems

• US 20050089890A1
• Filed: 06/21/2004
• Published: 04/28/2005
• Est. Priority Date: 05/20/1998
• Status: Abandoned Application

• Current Assignee: Roger S. Cubicciotti
• Original Assignee: Roger S. Cubicciotti
• Inventors: Cubicciotti, Roger S.
• Application Number:
  US10/872,973
• Publication Number:
  US 20050089890A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: Y10S 977/853 Biological sample

Abstract

Multimolecular devices and drug delivery systems prepared from synthetic heteropolymers, heteropolymeric discrete structures, multivalent heteropolymeric hybrid structures, aptameric multimolecular devices, multivalent imprints, tethered specific recognition devices, paired specific recognition devices, nonaptameric multimolecular devices and immobilized multimolecular structures are provided, including molecular adsorbents and multimolecular adherents, adhesives, transducers, switches, sensors and delivery systems. Methods for selecting single synthetic nucleotides, shape-specific probes and specifically attractive surfaces for use in these multimolecular devices are also provided. In addition, paired nucleotide-nonnucleotide mapping libraries for transposition of selected populations of selected nonoligonucleotide molecules into selected populations of replicatable nucleotide sequences are described.

Claims

1. A synthetic heteropolymer comprising:

a first synthetic defined sequence segment capable of specifically recognizing and covalently attaching a first selected nonoligonucleotide molecule; and

a second defined sequence segment attached to the first synthetic defined sequence segment with the proviso that the second defined sequence segment is not a fixed, unconjugated primer-annealing sequence.

2. The synthetic heteropolymer of claim 1 wherein the first synthetic defined sequence segment is attached to the second defined sequence segment via a nucleotide spacer.

3. The synthetic heteropolymer of claim 1 wherein the first synthetic defined sequence segment is attached to the second defined sequence segment via a nonnucleotide linker.

4. The synthetic heteropolymer of claim 1 wherein the first selected nonoligonucleotide molecule comprises a specific binding partner of the first synthetic defined sequence segment.

5. The synthetic heteropolymer of claim 1 wherein the first selected nonoligonucleotide molecule comprises a specifically attractive surface feature.

6. The synthetic heteropolymer of claim 1 wherein the second defined sequence segment is capable of specifically recognizing a second selected nonoligonucleotide molecule or a selected nucleic acid sequence.

7. The synthetic heteropolymer of claim 6 wherein the second selected nonoligonucleotide molecule comprises a specific binding partner of the second defined sequence segment.

8. The synthetic heteropolymer of claim 6 wherein the second selected nonoligonucleotide molecule comprises a specifically attractive surface feature.

9. The synthetic heteropolymer of claim 1 wherein the second defined sequence segment is capable of hybridizing to a selected nucleic acid sequence.

10. The synthetic heteropolymer of claim 1 wherein the second defined sequence segment is a conjugated defined sequence segment.

11. A multimolecular transducer comprising the synthetic heteropolymer of claim 1.

12. A multimolecular switch comprising the synthetic heteropolymer of claim 1.

13. A multimolecular sensor comprising the synthetic heteropolymer of claim 1.

14. A multimolecular delivery system comprising the synthetic heteropolymer of claim 1.

15. A multivalent multimolecular structure comprising a multivalent imprint of the synthetic heteropolymer of claim 1.

16. The multivalent multimolecular structure of claim 15 wherein the multivalent imprint is an idiotypic mimetic.

17. The multivalent multimolecular structure of claim 15 wherein the multivalent imprint is an antiidiotypic imprint.

18. A heteropolymeric discrete structure comprising a synthetic aptamer and a defined sequence segment attached to the synthetic aptamer.

19. The heteropolymeric discrete structure of claim 18 wherein the defined sequence segment comprises an aptamer, a nucleotide sequence which specifically binds or hybridizes to a selected nucleic acid sequence, or a conjugated defined sequence segment.

20. The heteropolymeric discrete structure of claim 18 wherein the synthetic aptamer comprises a shape-specific recognition element.

21. The heteropolymeric discrete structure of claim 18 wherein the defined sequence segment is attached to the synthetic aptamer via a nucleotide spacer.

22. The heteropolymeric discrete structure of claim 18 wherein the defined sequence segment is attached to the synthetic aptamer via a nonnucleotide linker.

23. A multimolecular transducer comprising the heteropolymeric discrete structure of claim 18.

24. A multimolecular switch comprising the heteropolymeric discrete structure of claim 18.

25. A multimolecular sensor comprising the heteropolymeric discrete structure of claim 18.

26. A multimolecular delivery system comprising the heteropolymeric discrete structure of claim 18.

27. A multivalent multimolecular structure comprising a multivalent imprint of the heteropolymeric discrete structure of claim 18.

28. The multivalent multimolecular structure of claim 27 wherein the multivalent imprint is an idiotypic mimetic.

29. The multivalent multimolecular structure of claim 27 wherein the multivalent imprint is an antiidiotypic imprint.

30. A molecular adsorbent comprising a solid phase and a multivalent template comprising a first specific recognition element specifically attached via the first specific recognition element to the solid phase wherein the solid phase comprises an amphibious or specifically attractive surface.

31. The molecular adsorbent of claim 30 wherein the multivalent template further comprises at least a second specific recognition element capable of specifically recognizing a selected nonoligonucleotide molecule.

32. The molecular adsorbent of claim 30 wherein the multivalent template further comprises at least a second specific recognition element capable of specifically hybridizing a selected nucleic acid sequence.

33. A multimolecular adherent comprising a specific recognition element and a first selected molecule attached to the specific recognition element wherein the specific recognition element specifically attaches via specific binding or shape-specific recognition the first selected molecule to a second selected molecule of an amphibious or specifically attractive surface.

34. The multimolecular adherent of claim 33 wherein the second selected molecule comprises a specific binding partner of the specific recognition element.

35. The multimolecular adherent of claim 33 wherein the second selected molecule comprises a specifically attractive surface feature.

36. A multimolecular adhesive comprising at least two specific recognition elements capable of specifically attaching and joining at least two surfaces wherein at least one of the specific recognition elements specifically recognizes an amphibious or specifically attractive surface.

37. The multimolecular adhesive of claim 36 wherein at least one of the specific recognition elements specifically binds to a selected molecule of an amphibious surface.

38. The multimolecular adhesive of claim 36 wherein at least one of the specific recognition elements specifically recognizes a surface feature of a specifically attractive surface.

39. The multimolecular adhesive of claim 36 wherein at least one of the specific recognition elements hybridizes to a nucleic acid sequence immobilized to the amphibious or specifically attractive surface.

40. A multivalent heteropolymeric hybrid structure comprising a first synthetic heteropolymer hybridizably linked to a second synthetic heteropolymer wherein each synthetic heteropolymer comprises at least two defined sequence segments and at least one defined sequence segment of the first synthetic heteropolymer specifically recognizes a selected nonoligonucleotide molecule.

41. The multivalent heteropolymeric hybrid structure of claim 40 wherein the selected nonoligonucleotide molecule comprises a specific binding partner of the at least one defined sequence segment of the first synthetic heteropolymer.

42. The multivalent heteropolymeric hybrid structure of claim 40 wherein the selected nonoligonucleotide molecule comprises a specifically attractive surface feature specifically recognized by the at least one defined sequence segment of the first synthetic heteropolymer.

43. The multivalent heteropolymeric hybrid structure of claim 40 wherein at least one defined sequence segment of the second synthetic heteropolymer specifically recognizes a second selected nonoligonucleotide molecule.

44. The multivalent heteropolymeric hybrid structure of claim 43 wherein the second selected nonoligonucleotide molecule comprises a specific binding partner of the at least one defined sequence segment of the second synthetic heteropolymer.

45. The multivalent heteropolymeric hybrid structure of claim 43 wherein the second selected nonoligonucleotide molecule comprises a specifically attractive surface feature specifically recognized by the at least one defined sequence segment of the second synthetic heteropolymer.

46. The multivalent heteropolymeric hybrid structure of claim 40 wherein at least one defined sequence segment of the second synthetic heteropolymer specifically binds a selected nucleic acid sequence.

47. The multivalent heteropolymeric hybrid structure of claim 40 wherein the at least two defined sequence segments of the second synthetic heteropolymer hybridize to selected nucleic acid sequences.

48. The multivalent heteropolymeric hybrid structure of claim 40 wherein at least one defined sequence segment of the second synthetic heteropolymer comprises a conjugated defined sequence segment.

49. A multimolecular transducer comprising the multivalent heteropolymeric hybrid structure of claim 40.

50. A multimolecular switch comprising the multivalent heteropolymeric hybrid structure of claim 40.

51. A multimolecular sensor comprising the multivalent heteropolymeric hybrid structure of claim 40.

52. A multimolecular delivery system comprising the multivalent heteropolymeric hybrid structure of claim 40.

53. A multivalent multimolecular structure comprising a multivalent imprint of the multivalent heteropolymeric hybrid structure of claim 40.

54. The multivalent multimolecular structure of claim 53 wherein the multivalent imprint is an idiotypic mimetic.

55. The multivalent multimolecular structure of claim 53 wherein the multivalent imprint is an antiidiotypic imprint.

56. An aptameric multimolecular device comprising a nonaptameric specific recognition pair and a synthetic aptamer which specifically binds or shape-specifically recognizes an aptamer target wherein a member of the nonaptameric specific recognition pair is conjugated to the aptamer to form a conjugated aptamer.

57. The aptameric multimolecular device of claim 56 wherein the conjugated aptamer is capable of positioning the aptamer target for functional coupling with a member of the nonaptameric specific recognition pair.

58. The aptameric multimolecular device of claim 56 wherein the conjugated aptamer or the aptamer target further comprises an effector molecule.

59. The aptameric multimolecular device of claim 56 wherein the nonaptameric specific recognition pair comprises a nucleotide ligand or nucleotide receptor.

60. The aptameric multimolecular device of claim 56 wherein the aptamer target comprises a surface feature of a specifically attractive surface.

61. A multimolecular transducer comprising the aptameric multimolecular device of claim 56.

62. A multimolecular switch comprising the aptameric multimolecular device of claim 56.

63. A multimolecular sensor comprising the aptameric multimolecular device of claim 56.

64. A multimolecular delivery system comprising the aptameric multimolecular device of claim 56.

65. A multivalent multimolecular structure comprising a multivalent imprint of the aptameric multimolecular device of claim 56.

66. The multivalent multimolecular structure of claim 65 wherein the multivalent imprint is an idiotypic mimetic.

67. The multivalent multimolecular structure of claim 65 wherein the multivalent imprint is an antiidiotypic imprint.

68. A tethered specific recognition device comprising a molecular scaffold and at least two members of a specific binding pair or shape-specific recognition pair wherein the members of the specific binding pair or shape-specific recognition pair are covalently or pseudoirreversibly attached to the molecular scaffold.

69. The tethered specific recognition device of claim 68 wherein the at least two members of the specific binding pair or shape-specific recognition pair are specifically and directly attached to each other.

70. The tethered specific recognition device of claim 68 wherein at least one member of the specific binding pair or shape-specific recognition pair comprises an effector molecule.

71. The tethered specific recognition device of claim 68 wherein the molecular scaffold comprises a nonnucleotide molecule.

72. The tethered specific recognition device of claim 68 wherein the molecular scaffold comprises a replicatable nucleotide.

73. The tethered specific recognition device of claim 68 wherein at least one member of the specific binding pair or shape-specific recognition pair comprises an aptamer.

74. A tethered specific recognition device comprising a molecular scaffold and at least four members of at least two specific recognition pairs wherein each member is covalently or pseudoirreversibly attached to the molecular scaffold.

75. The tethered specific recognition device of claim 74 wherein at least one of the two specific recognition pairs comprises a specific binding pair.

76. The tethered specific recognition device of claim 74 wherein at least one of the two specific recognition pairs comprises a shape-specific recognition pair.

77. The tethered specific recognition device of claim 74 wherein at least one of the two specific recognition pairs comprises hybridizable selected nucleic acid sequences.

78. The tethered specific recognition device of claim 74 wherein specific attachment of the two members of one specific recognition pair precludes specific attachment of the two members of another specific recognition pair.

79. A paired specific recognition device comprising a molecular scaffold and at least two different specific recognition pairs conjugated to the molecular scaffold wherein at least one specific recognition pair is capable of specific binding or shape-specific recognition.

80. The paired specific recognition device of claim 79 wherein the molecular scaffold is capable of positioning the at least two specific recognition pairs for functional coupling between at least two members of the at least two specific recognition pairs.

81. The paired specific recognition device of claim 79 wherein at least one member of one of the at least two specific recognition pairs comprises an effector molecule.

82. The paired specific recognition device of claim 79 wherein the molecular scaffold comprises a nonnucleotide molecule.

83. The paired specific recognition device of claim 79 wherein the molecular scaffold comprises a replicatable nucleotide.

84. The paired specific recognition device of claim 79 wherein at least one member of the at least two specific recognition pairs comprises an aptamer.

85. The paired specific recognition device of claim 79 wherein at least one member of the two specific recognition pairs is specifically and directly attached to its specific recognition partner.

86. A multimolecular transducer comprising the paired specific recognition device of claim 79.

87. A multimolecular switch comprising the paired specific recognition device of claim 79.

88. A multimolecular sensor comprising the paired specific recognition device of claim 79.

89. A multimolecular delivery system comprising the paired specific recognition device of claim 79.

90. A multivalent multimolecular structure comprising a multivalent imprint of the paired specific recognition device of claim 79.

91. The multivalent multimolecular structure of claim 90 wherein the multivalent imprint is an idiotypic mimetic.

92. The multivalent multimolecular structure of claim 90 wherein the multivalent imprint is an antiidiotypic imprint.

93. A nonaptameric multimolecular device comprising a conjugated defined sequence segment and at least two different specific binding pairs or shape-specific recognition pairs wherein one member of each specific binding pair or shape-specific recognition pair is conjugated to the conjugated defined sequence segment.

94. The nonaptameric multimolecular device of claim 93 wherein the conjugated defined sequence segment is capable of positioning the specific binding pairs or shape-specific recognition pairs for functional coupling between at least two members of the specific binding pairs or shape-specific recognition pairs.

95. The nonaptameric multimolecular device of claim 93 wherein the conjugated member of at least one of the specific binding pairs or shape-specific recognition pairs comprises a modified nucleotide.

96. The nonaptameric multimolecular device of claim 93 wherein the conjugated member of at least one of the specific binding pairs or shape-specific recognition pairs comprises a nucleotide ligand or nucleotide receptor.

97. A multimolecular transducer comprising the nonaptameric multimolecular device of claim 93.

98. A multimolecular switch comprising the nonaptameric multimolecular device of claim 93.

99. A multimolecular sensor comprising the nonaptameric multimolecular device of claim 93.

100. A multimolecular delivery system comprising the nonaptameric multimolecular device of claim 93.

101. A multivalent multimolecular structure comprising a multivalent imprint of the nonaptameric multimolecular device of claim 93.

102. The multivalent multimolecular structure of claim 101 wherein the multivalent imprint is an idiotypic mimetic.

103. The multivalent multimolecular structure of claim 101 wherein the multivalent imprint is an antiidiotypic imprint.

104. A shape-specific probe comprising a nucleotide-based or nonnucleotide recognition element capable of recognizing a specifically attractive surface feature.

105. The shape-specific probe of claim 104 wherein the recognition element comprises an aptamer.

106. The shape-specific probe of claim 104 wherein the recognition element comprises a nucleotide ligand or nucleotide receptor.

107. The shape-specific probe of claim 104 wherein the recognition element comprises a selectable nonoligonucleotide molecule.

108. A multimolecular structure comprising the shape-specific probe of claim 104.

109. A multivalent imprint of a multimolecular structure comprising at least two specific recognition elements imprinted from the multimolecular structure.

110. The multivalent imprint of claim 109 wherein the imprinted specific recognition elements from the multimolecular structure mimic the at least two specific recognition elements of the multimolecular structure.

111. The multivalent imprint of claim 109 wherein the imprinted specific recognition elements from the multimolecular structure are capable of specifically recognizing the at least two specific recognition elements of the multimolecular structure.

112. A paired nucleotide-nonnucleotide mapping library comprising a plurality of selected specific recognition partners capable of transposing a selected population of selected nonoligonucleotide molecules into replicatable nucleotide sequences.

113-123. -123. (canceled)

124. A method for identifying a specifically attractive surface feature comprising:

(a) contacting a surface library with a selected shape-specific recognition partner; and

(b) detecting attachment of the selected shape-specific recognition partner to a specifically attractive surface feature of the surface library.

125. The method of claim 124 wherein the shape-specific recognition partner is detectably labeled.

126. The method of claim 124 wherein attachment is detected by single-molecule detection.

127. The method of claim 126 wherein single-molecule detection is performed by scanning probe microscopy.

128. An immobilized multimolecular structure comprising a solid support and a multimolecular structure immobilized to the solid support wherein the multimolecular structure is selected from the group consisting of aptameric multimolecular devices, heteropolymeric discrete structures, multivalent heteropolymeric hybrid structures, synthetic heteropolymers, tethered specific recognition devices, paired specific recognition devices, nonaptameric multimolecular devices, multivalent molecular structures, multivalent imprints, and multimolecular drug delivery systems.

129. A multimolecular drug delivery system comprising a multimolecular structure selected from a group consisting of aptameric multimolecular devices, heteropolymeric discrete structures, multivalent heteropolymeric hybrid structures, synthetic heteropolymers, tethered specific recognition devices, paired specific recognition devices, nonaptameric multimolecular devices, multivalent imprints, and immobilized multimolecular delivery systems wherein the multimolecular structure contains a synthetic receptor that specifically recognizes a drug or a selected target.