Single-molecule selection methods and compositions therefrom
First Claim
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.
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Abstract
Single-molecule selection methods are provided for identifying target-binding molecules from diverse sequence and shape libraries. Complexes and imprints of selected target-binding molecules are also provided. The subject selection methods are used to identify oligonucleotide and nonnucleotide molecules with desirable properties for use in pharmaceuticals, drug discovery, drug delivery, diagnostics, medical devices, cosmetics, agriculture, environmental remediation, smart materials, packaging, microelectronics and nanofabrication. Single oligonucleotide molecules with desirable binding properties are selected from diverse sequence libraries and identified by amplification and sequencing. Alternatively, selected oligonucleotide molecules are identified by sequencing without amplification. Nonnucleotide molecules with desirable properties are identified by single-molecule selection from libraries of conjugated molecules or nucleotide-encoded nonnucleotide molecules. Alternatively, target-specific nonnucleotide molecules are prepared by imprinting selected oligonucleotide molecules into nonnucleotide molecular media. Complexes and imprints of molecules identified by single-molecule selection are shown to have broad utility as drugs, prodrugs, drug delivery systems, willfully reversible cosmetics, diagnostic reagents, sensors, transducers, actuators, adhesives, adherents and novel multimolecular devices.
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Citations
129 Claims
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1. A synthetic heteropolymer comprising:
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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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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18. A heteropolymeric discrete structure comprising a synthetic aptamer and a defined sequence segment attached to the synthetic aptamer.
- 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.
- 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.
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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.
- 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.
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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.
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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.
- 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.
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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.
- 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.
- 104. A shape-specific probe comprising a nucleotide-based or nonnucleotide recognition element capable of recognizing a specifically attractive surface feature.
- 109. A multivalent imprint of a multimolecular structure comprising at least two specific recognition elements imprinted from the multimolecular structure.
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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.
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113. A method for selecting a single synthetic nucleotide molecule capable of recognizing a selected target molecule comprising detecting a signal resulting from the proximity or functional coupling between the single synthetic nucleotide and the selected target molecule.
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124. A method for identifying a specifically attractive surface feature comprising:
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(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.
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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.
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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.
Specification