New functionalised linkers for targeted proteolysis
Proteolysis targeting chimeras (PROTACs) are small molecules that induce degradation of a target protein, enabling the design of chemical probes and therapeutic agents for previously unreachable proteins. PROTACs are heterobifunctional molecules containing binding ligands to an E3 ubiquitin ligase and a protein of interest, connected by a linker. The formation of a ternary complex of target protein, PROTAC and E3 ligase results in ubiquitination of the target protein followed by degradation in the proteasome. The goal of the EU-funded PREDICT project is to identify and test novel functional linker motifs which will tune up interactions within the ternary complex. The effects of new PROTAC linkers will be systematically studied and used as the basis to design novel functionalised linkers.