An ultrasonically sensitive small-molecule chimera for sono-controllable proteolysis

We herein report an ultrasonically sensitive small-molecule chimera (USC) as a monospecific and conditional protein degrader. The USC comprises a bromodomain-containing protein 4 (BRD4) ligand conjugated with a sonosensitizer through a short linker. After ligand-guided anchoring onto BRD4 and sonoirradiation, the USC produces singlet oxygen to trigger protein degradation. The superiority of ultrasound to near-infrared light in terms of inducing deep-tissue proteolysis is also demonstrated.