Interaction-dependent PCR: Identification of ligand-target pairs from libraries of ligands and libraries of targets in a single solution-phase experiment

Abstract: Interaction-dependent PCR (IDPCR) is a solution-phase method to identify binding partners from combined libraries of small-molecule ligands and targets in a single experiment. Binding between DNA-linked targets and DNA-linked ligands induces formation of an extendable duplex. Extension links codes that identify the ligand and target into one selectively amplifiable DNA molecule. In a model selection, IDPCR resulted in the enrichment of DNA encoding all five known protein-ligand pairs out of 67 599 possible sequences. Recent advances in genome and proteome research have led to a dramatic increase in the number of macromolecular targets of interest to the life sciences. The rapid identification of ligands to this expanding number of targets is a major scientific and techno-logical challenge. To this end, a variety of target-oriented high-throughput screening methods have been developed. Two funda