Free reactant use in nucleic acid-templated synthesis
First Claim
1. A method of synthesizing a reaction product, the method comprising the steps of:
- (a) providing a mixture comprising a first reactive unit and a second reactive unit under conditions to induce a reaction between the first and second reactive units to produce a reaction intermediate;
(b) providing an oligonucleotide comprising an identifying sequence covalently attached to the reaction intermediate; and
(c) combining the reaction intermediate with a free reactant selectively reactive with the reaction intermediate, thereby synthesizing a reaction product linked to the identifying sequence, wherein the free reactant is more reactive with the reaction intermediate than with at least one of the reactive units in the starting mixture.
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Abstract
The present invention provides methods and compositions for expanding the scope of chemical reactions that can be performed during nucleic acid-templated organic syntheses. In particular, nucleic acid-templated chemistries are used to produce reaction intermediates attached to an oligonucleotide that can be used to identify the reaction intermediates and/or the resulting reaction products. The reaction intermediates then are reacted with free reactants (for example, reactants that are difficult or impractical to couple to an oligonucleotide) to produce a reaction product. This approach expands the scope of reagents useful in nucleic acid-templated syntheses to reagents that do not need to be or cannot be tethered to an oligonucleotide. The reagents, however, still permit the synthesis of reaction products attached to oligonucleotides that can be used to identify the reaction products.
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Citations
45 Claims
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1. A method of synthesizing a reaction product, the method comprising the steps of:
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(a) providing a mixture comprising a first reactive unit and a second reactive unit under conditions to induce a reaction between the first and second reactive units to produce a reaction intermediate;
(b) providing an oligonucleotide comprising an identifying sequence covalently attached to the reaction intermediate; and
(c) combining the reaction intermediate with a free reactant selectively reactive with the reaction intermediate, thereby synthesizing a reaction product linked to the identifying sequence, wherein the free reactant is more reactive with the reaction intermediate than with at least one of the reactive units in the starting mixture. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10-32. -32. (canceled)
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33. A method of synthesizing a reaction product by nucleic acid-templated synthesis, the method comprising the steps of:
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(a) providing a mixture comprising a plurality of first reactive units attached to first oligonucleotides comprising codon sequences, wherein the oligonucleotide sequence is indicative of the first reactive unit attached thereto;
(b) providing a second reactive unit attached to a second oligonucleotide comprising an anti-codon sequence complementary to the codon sequence of at least one first reactive unit;
(c) annealing the codon sequence of at least one of the first oligonucleotides with the anti-codon sequence of the second oligonucleotide to induce a reaction between the first and second reactive units to form a first reaction intermediate attached at least to a first oligonucleotide; and
(d) combining the first reaction intermediate with a free reactant selectively reactive with the first reaction intermediate, thereby synthesizing a first reaction product attached to the first oligonucleotide, wherein the free reactant is more reactive with the first reaction intermediate than with at least one of the reactive units in the mixture. - View Dependent Claims (34)
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35. An in vitro method of performing nucleic acid-templated synthesis, the method comprising the steps of:
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(a) providing (i) a template comprising a first reactive unit covalently attached to a first oligonucleotide defining a codon sequence, and (ii) a transfer unit comprising a second reactive unit covalently attached to a second oligonucleotide defining an anti-codon sequence complementary to the codon sequence of the template;
(b) annealing the codon and anti-codon sequences to bring the first reactive unit and the second reactive unit into reactive proximity so that the first and second reactive units react with one another to produce a reaction intermediate; and
(c) contacting the reaction intermediate with a free reactant, which chemically reacts with the reaction intermediate to produce a reaction product, wherein the first oligonucleotide remains attached to the reaction product. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44, 45)
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Specification