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Published on: November 9, 2020
An ultrasonically sensitive small-molecule chimera for sono-controllable proteolysis
Bin Zhang1, Siyi Wang1, Chen Li1
1State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center at Nanjing University, Nanjing University, Nanjing 210023, China. njuzy@nju.edu.cn.
Abstract:
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.

