Compositions, methods, and kits for identifying candidate molecules from encoded chemical libraries

1. A method for identifying a candidate molecule from a library of tagged chemicals, which comprises the steps of:

a) probing a target molecule with a library of chemical compositions, wherein each composition in the library comprises:

i) a microscopic bead;

ii) a plurality of identical copies of a single-species, sequenceable molecule produced by at least one of BEAMing PCR or bridge amplification, each operably connected to said microscopic bead; and

iii) a tag sequence comprising DNA, modified DNA or RNA, which tag sequence is complementary to, and is hybridized to, said sequenceable molecule,

iv) a candidate chemical operably connected to said tag sequence,

wherein said tag sequence is a unique identifier for its connected candidate chemical;

b) isolating each composition which binds to said target molecule;

c) sequencing said sequenceable molecule from each said composition;

d) identifying, by hybridization under highly stringent conditions, the tag sequence which complements and hybridizes to the identified sequence of said sequenceable molecule; and

e) identifying, from a database correlating said tag sequence to its connected candidate chemical, the candidate molecule.

2. The method of claim 1 , wherein said candidate chemical is produced by template-directed synthesis using said tag sequence as the template.

3. The method of claim 2 , wherein said tag sequence is DNA.

4. The method of claim 2 , wherein said tag sequence is operably connected to said candidate chemical by a covalent bond.

5. The method of claim 1 , wherein said tag sequence is bound to said candidate chemical during or after the synthesis of said candidate chemical,

provided that said candidate chemical is not produced by template-directed synthesis using said tag sequence as the template.

6. The method of claim 5 , wherein said tag sequence is DNA.

7. The method of claim 5 , wherein said tag sequence is operably connected to said candidate chemical by a covalent bond.

8. The method of claim 1 , wherein said hybridization of said tag sequence and said sequenceable molecule occurs only under highly stringent conditions.

9. The method of claim 1 , wherein said sequenceable molecule is DNA.

10. The method of claim 1 , wherein said sequenceable molecule is operably connected to said microscopic bead by a ligand-binding partner pair.

11. The method of claim 10 , wherein said ligand-binding partner pair is biotin and one or more biotin ligands selected from the group consisting of avidin, streptavidin, and neutravidin.

12. The method of claim 1 , wherein said sequencing the sequenceable molecule is selected from the group consisting of polymerase chain reaction, reverse-transcriptase polymerase chain reaction, or modified polymerase chain reaction.

13. The method of claim 1 , wherein said microscopic bead is between 10 nanometers and 30 microns.

14. The method of claim 13 , wherein said microscopic bead is between 100 nanometers and 1 micron.

15. The method of claim 1 , wherein said microscopic bead comprises glass, plastic, acrylic copolymers, cellulose, nylon, dextran, latex, or polyacrolein.

16. The method of claim 15 , wherein said microscopic bead comprises polystyrene.

17. The method of claim 1 , comprising between steps (b) and (c) the additional steps of:

i) isolating the single-species, sequenceable molecule from each said composition which binds to said target molecule; and

ii) amplifying said sequenceable molecule.

18. The method of claim 17 , wherein said amplifying the sequenceable molecule is polymerase chain reaction.

19. The method of claim 1 , wherein said plurality of identical copies of a single-species, sequenceable molecule are produced by BEAMing PCR.

20. The method of claim 19 , wherein said tag sequence comprises DNA and said sequenceable molecule comprises DNA.

21. A method for producing a one-bead-one-sequence composition, which comprises the steps of:

(a) generating a microscopic-bead-bound sequenceable molecule by at least one of BEAMing PCR or bridge amplification;

(b) hybridizing said microscopic-bead-bound sequenceable molecule to a tag sequence comprising DNA, modified DNA or RNA, which tag sequence uniquely identifies and is covalently connected to a candidate chemical.

22. The method of claim 21 , wherein said hybridization of said tag sequence and said microscopic-bead-bound sequenceable molecule occurs only under highly stringent conditions.

23. The method of claim 22 , wherein:

said tag sequence is operably connected to said candidate chemical by a covalent bond; and

said sequenceable molecule is selected from the group consisting of DNA, modified DNA, and RNA.

24. The method of claim 23 , wherein said microscopic bead is magnetic.

25. The method of claim 21 , wherein said generating step is carried out by BEAMing PCR.

26. The method of claim 25 , wherein said tag sequence comprises DNA and said sequenceable molecule comprises DNA.

27. A method for identifying a candidate molecule from a library of tagged chemicals, which comprises the steps of:

a) probing a target molecule with a library of chemical compositions, wherein each composition in the library comprises:

i) a microscopic bead;

ii) a plurality of identical copies of a single-species, DNA sequenceable molecule produced by at least one of BEAMing PCR or bridge amplification, each operably connected to said microscopic bead by a ligand-binding partner pair; and

iii) a tag sequence comprising DNA, modified DNA or RNA, which tag sequence is complementary to, and is hybridized to, said sequenceable molecule,

iv) a candidate chemical operably connected to said tag sequence by covalent bond, wherein said candidate chemical is produced by template-directed synthesis using said tag sequence as the template, and wherein said tag sequence is a unique identifier for its connected candidate chemical;

b) isolating each composition which binds to said target molecule;

c) isolating the single-species, sequenceable molecule from each said composition which binds to said target molecule; and

d) amplifying by polymerase chain reaction said sequenceable molecule;

e) sequencing by polymerase chain reaction said sequenceable molecule from each said composition;

f) identifying, by hybridization under highly stringent conditions, the tag sequence which complements and hybridizes to the identified sequence of said sequenceable molecule; and

g) identifying, from a database correlating said tag sequence and its connected candidate chemical, the candidate molecule.

28. The method of claim 27 , wherein said plurality of identical copies of a single-species, sequenceable molecule are produced by BEAMing PCR.

29. The method of claim 28 , wherein said tag sequence comprises DNA and said sequenceable molecule comprises DNA.