Patent ID: 6919178
Filing Date: 2005-07-19
Classification: C07B,C07D,C40B,G01N

Abstract:
1. A process comprising the steps of: (i) contacting a Target Biological Molecule (TBM) having a first and a second site of interest, and containing or modified to contain a nucleophile, selected from the group consisting of thiol, protected thiol, reversible disulfide, hydroxyl, protected hydroxyl, amino, protected amino, carboxyl and protected carboxyl groups, at or near the first site of interest, with a plurality of first organic ligand candidates, said candidates having a functional group reactive with the nucleophile, under conditions such that a reversible covalent bond is formed between the nucleophile and a candidate that has affinity for the first site of interest, to form a TMB-first ligand complex; (ii) identifying the first ligand from the TBM-first ligand complex; (iii) designing a derivative of the first ligand identified in (ii) to provide a small molecule extender (SME) having a first functional group reactive with the nucleophile on the TBM and a second functional group reactive with a second ligand having affinity for the second site of interest, wherein said first functional group is capable of forming an irreversible covalent group with the thiol, protected thiol, reversible disulfide bond, hydroxyl, protected hydroxyl, amino, protected amino, carboxyl or protected carboxyl group on said TBM; (iv) contacting the SME with the TBM to form a TBM-SME complex, and (v) contacting the TBM-SME complex with a plurality of second small organic ligand candidates, said candidates having a functional group reactive with the SME in said TBM-SME complex, wherein a candidate that has affinity for said second site of interest on said TBM forms a reversible covalent bond with said TBM-SME complex, whereby a second ligand is identified.