Evolving new molecular function

A method for selecting small molecules having binding affinity to a target molecule, the method comprising:

• (a) producing a library of small molecules covalently attached to corresponding oligonucleotides by annealing first oligonucleotides covalently attached to first reactive units with second oligonucleotides covalently attached to second reactive units to bring the first reactive units and the second reactive units into reactive proximity thereby to produce the small molecules, wherein each of the corresponding oligonucleotides has a nucleotide sequence informative of the synthetic history of the small molecule associated therewith:
• (b) mixing a target molecule with the small molecules covalently attached to corresponding oligonucleotides under conditions to permit the small molecules capable of binding the target molecule to bind thereto;
• (c) separating small molecules that bind to the target molecule from unbound small molecules;
• (d) mutating the sequences of the oligonucleotides associated with the separated small molecules;
• and
• (e) using the mutated sequences to direct synthesis of a new library of small molecules.

A method for selecting one or more small molecules having binding affinity to a target molecule, the method comprising:

• (a) producing a library of small molecules associated with corresponding oligonucleotides by a method comprising the steps of
• (i) providing a plurality of templates comprising a plurality of first reactive units associated with a corresponding plurality of first oligonucleotides, wherein each first oligonucleotide defines at least one codon sequence,
• (ii) providing a plurality of transfer units comprising a plurality of second reactive units covalently attached to a corresponding plurality of second oligonucleotides, wherein each second oligonucleotide defines an anti-codon sequence complementary to a codon sequence, and
• (iii) annealing oligonucleotides having complementary codon and anti-codon sequences to bring the first and second reactive units into reactive proximity thereby producing the small molecules associated with the corresponding oligonucleotides, wherein each of the corresponding oligonucleotides has a nucleotide sequence informative of the structure of the small molecule associated therewith;
• (b) mixing the small molecules with a target molecule under conditions to permit small molecules capable of binding the target molecule to bind thereto;
• and
• (c) separating small molecules that bind to the target molecule from unbound small molecules thereby selecting one or more molecules having binding affinity to the target molecule.

A method for selecting small molecules having binding affinity to a target molecule, the method comprising:

• (a) producing a library of small molecules covalently attached to corresponding oligonucleotides by annealing first oligonucleotides covalently attached to first reactive units with second oligonucleotides covalently attached to second reactive units to bring the first reactive units and the second reactive units into reactive proximity thereby to produce the small molecules, wherein each of the corresponding oligonucleotides has a nucleotide sequence informative of the structure of the small molecule associated therewith;
• (b) mixing a target molecule with the small molecules covalently attached to corresponding oligonucleotides under conditions to permit the small molecules capable of binding the target molecule to bind thereto;
• (c) separating small molecules that bind to the target molecule from unbound small molecules;
• (d) mutating the sequences of the oligonucleotides associated with the separated small molecules;
• and
• (e) using the mutated sequences to direct synthesis of a new library of small molecules.

A method for evolving a library of small molecules, the method comprising:

• (a) producing a library of small molecules covalently attached to corresponding oligonucleotides by annealing first oligonucleotides covalently attached to first reactive units with second oligonucleotides covalently attached to second reactive units to bring the first reactive units and the second reactive units into reactive proximity to produce the small molecules, wherein each of said corresponding oligonucleotide has a nucleotide sequence informative of the synthetic history of the small molecule associated therewith;
• (b) selecting the oligonucleotides associated with the small molecules having a desired property;
• (c) mutating the sequences of the selected oligonucleotides;
• and
• (d) synthesizing a new library of small molecules using the mutated sequences.

A method for evolving a library of small molecules, the method comprising:

• (a) producing a library of small molecules covalently attached to corresponding oligonucleotides by annealing first oligonucleotides covalently attached to first reactive units with second oligonucleotides covalently attached to second reactive units to bring the first reactive units and the second reactive units into reactive proximity to produce the small molecules, wherein each of said corresponding oligonucleotide has a nucleotide sequence informative of the structure of the small molecule associated therewith;
• (b) selecting the oligonucleotides associated with the small molecules having a desired property;
• (c) mutating the sequences of the selected oligonucleotides;
• and
• (d) synthesizing a new library of small molecules using the mutated sequences.

A method of selecting one or more small molecules having binding affinity to a target molecule, the method comprising:

• (a) producing a library of small molecules covalently attached to corresponding oligonucleotides by annealing first oligonucleotides covalently attached to first reactive units with second oligonucleotides covalently attached to second reactive units to bring the first reactive units and the second reactive units into reactive proximity thereby to produce the small molecules, wherein each said corresponding oligonucleotide attached to a small molecule has a nucleotide sequence informative of the structure or the synthetic history of the small molecule associated therewith;
• (b) mixing the small molecules with a target molecule under conditions to permit small molecules capable of binding the target to bind thereto;
• and
• (c) separating small molecules that bind to the target from unbound small molecules thereby selecting one or more small molecules having binding affinity to the target molecule.