Identification of ligand linkage vectors for the development of p300/CBP degraders.

To develop new degrader molecules from an existing protein ligand a linkage vector must be identified and then joined with a suitable E3 ligase without disrupting binding to the respective targets. This is typically achieved through empirically evaluating the degradation efficacy of a series of synthetic degraders. Our strategy for determining optimal linkage sites utilises biotinylated protein ligands, linked potential conjugation sites of an inhibitor to confirm whether target protein is maintained after forming a conjugate.