METHODS FOR RAPIDLY IDENTIFYING SMALL ORGANIC MOLECULE LIGANDS FOR BINDING TO BIOLOGICAL TARGET MOLECULES

摘要

The present invention is directed to novel methods for rapidly and unambiguously identifying small organic molecule ligands for binding to biological target molecules. Small organic molecule ligands identified according to the methods of the present invention may find use, for example, as novel therapeutic drug lead compounds, enzyme inhibitors, labeling compounds, diagnostic reagents, affinity reagents for protein purification, and the like. Also presented are novel methods for identifying high affinity binding ligands for a biological target molecule of interest, wherein those methods comprise linking two or more small organic molecule ligands previously identified as being capable of binding to the biological target molecule of interest. Biological target molecules include, for example, polypeptides, nucleic acids, carbohydrates, nucleoproteins, glycoproteins, glycolipids and lipoproteins.

主权项

1. A method for identifying an organic molecule ligand that binds to a site of interest on a biological target molecule, said method comprising:
(a) obtaining a biological target molecule that comprises or has been modified to comprise a chemically reactive group, wherein said site of interest on said target molecule comprises said chemically reactive group; (b) combining said target molecule with one or more members of a library of organic compounds that are capable of covalently bonding to said chemically reactive group, wherein at least one member of said library binds to said site of interest and forms a covalent bond with said chemically reactive group to form a target molecule/organic compound conjugate; and (c) identifying the organic compound that forms a covalent bond with said chemically reactive group.