An ultrasonic small-molecule chimera for sono-controllable proteolysis

Abstract

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