I-Corps Supplement to parent grant DNA Encoded Macrocycles Libraries As A Source of Protein-Protein Interaction Inhibitors

Project Summary Protein protein interactionsPPIsare at the heart of almost every biological processThereforethere is great interest in the discovery of chemical probes that potently and selectively antagonize PPIsThis generally requires chemical matter quite different than the Lipinski compliant small molecules typically employed to antagonize enzyme active sitesThis project will create a novel library of millions of DNA encodedcell permeable macrocycleswhich will serve as a rich source of PPI inhibitorsA model screen will be done to identify inhibitors of the interaction of Rpnand Uchtwo interesting proteins in the proteasomeDeluge will make this library and an optimized screening protocol available to customers in an easy to use formatempowering them to carry out their own screening campaignswith the company providing informatics and chemistry support afterwardsThis effort is expected to stimulate the discovery of interesting PPI inhibitors of interest to the biomedical research community in a way that is commercially attractive to Deluge Project Narrative There is currently intense interest in the discovery of chemical probes able to potently antagonize proteinprotein interactionsPPIsThe efforts described here will result in the creation of a high quality library of millions of novelDNA encodedcell permeable macrocyclesThis will be created in a format that can be provided to customers to carry out their own screens for PPI inhibitorsthusdemocratizingthis powerful technology and stimulating the rate of discovery of novel chemical probes