Evolving new molecular
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Abstract
Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.
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Citations
67 Claims
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1-46. -46. (canceled)
- 47. A library of chemical compounds, the library comprising small molecules associated with corresponding oligonucleotides, wherein the oligonucleotide has a nucleotide sequence informative of the synthetic history of the small molecule associated therewith:
- 53. A library of chemical compounds, the library comprising small molecules associated with corresponding oligonucleotides, wherein the oligonucleotide has a nucleotide sequence informative of the structure of the small molecule associated therewith.
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57. A library of chemical compounds prepared by the method comprising:
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(a) providing a library of chemical compounds, the chemical compounds being associated with corresponding oligonucleotides, wherein an oligonucleotide has a nucleotide sequence informative of the synthetic history of the chemical compound associated therewith;
(b) selecting the oligonucleotides associated with the chemical compounds having a desired property to a target molecule;
(c) mutating the sequences of the selected oligonucleotides; and
(d) synthesizing a new library of chemical compounds using the mutated sequences. - View Dependent Claims (58, 59, 60)
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- 61. An evolvable library of small molecules, the small molecules being associated with corresponding oligonucleotides having nucleotide sequences capable of directing synthesis of a new library of small molecules.
Specification