Target-directed Synthesis of Protein-Protein Interaction Inhibitors

Protein-protein interactions (PPIs) play critical roles in many biological pathways, the mis-regulation of which can result in disease. Therefore, PPIs have long been considered attractive drug targets, but the number of successful inhibitors generated remains limited. Current screening methods using established compound libraries often lack the structural properties necessary to identify inhibitors of the characteristically large and flat interfaces of most PPIs. We will combine the advantages of robotically enabled screening and a novel assay developed in the Armstrong and Mann groups to establish a high-throughput technology for the identification of PPI inhibitors with the target protein present in the screening conditions to enable it to select for its preferred ligands. This will enable the rapid identification of either peptide or small molecule ligands for any target PPI.