Encoded combinatorial chemical libraries

• US 5,573,905 A
• Filed: 03/30/1992
• Issued: 11/12/1996
• Est. Priority Date: 03/30/1992
• Status: Expired due to Term

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Brenner, Sydney, Lerner, Richard, Janda, Kim
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): CAMPBELL, EGGERTON A
• Application Number:
  US07/860,445
• Time in Patent Office: 1,688 Days
• Field of Search: 435/6, 435/7.94, 935/77, 935/78, 530/350, 436/501
• US Class Current: 435/6.16
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 15/1062 mRNA-Display, e.g. polypeptide and encoding template are connected covalently
• CPC Class Codes: C12N 15/1075 by coupling phenotype to genotype, not provided for in other groups of this subclass
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Abstract

The present invention describes an encoded combinatorial chemical library comprised of a plurality of bifunctional molecules having both a chemical polymer and an identifier oligonucleotide sequence that defines the structure of the chemical polymer. Also described are the bifunctional molecules of the library, and methods of using the library to identify chemical structures within the library that bind to biologically active molecules in preselected binding interactions.

Claims

1. A method for identifying a biochemical polymer that participates in a preselected binding interaction with a biologically active molecule to form a binding reaction complex, the method comprising the steps of:

a) providing a library of bifunctional molecules, each bifunctional molecule having the formula A-B-C, wherein A is the biochemical polymer, B is a linker molecule operatively linked to A and C, and C is an identifier oligonucleotide comprising a sequence of nucleotides which encodes and identifies the biochemical polymer A;

then

b) admixing in solution said library of bifunctional molecules of said step (a) with the biologically active molecule under binding conditions for a time period sufficient to form the binding reaction complex;

then

c) isolating the bindinq reaction complex formed in said step (b);

then

d) amplifying the identifier oligonucleotide C of the bifunctional molecule within the binding reaction complex isolated in said step (c) by means of PCR; and

then

e) sequencing and decoding the identifier oligonucleotide C amplified in said step (d) for identifying the biochemical polymer that participated in the preselected binding interaction.

2. The method of claim 1 wherein said biologically active molecule is affixed to a solid support.

3. The method of claim 1 wherein said biologically active molecule is operatively linked to a binding means capable of binding a binder molecule.

4. The method of claim 3 wherein said binding means is selected from the group consisting of biotin, protein A and magnetic beads.

5. The method of claim 1 wherein said step

(d) comprises the following substeps:

i) amplifying the identifier oligonucleotide C isolated in said step (c) by a polymerase chain reaction (PCR); and

then

ii) sequencing and decoding the PCR amplification product of said substep i for identifying the biochemical polymer that participated in the preselected binding interaction.