Fig. 1: Demonstration of catalytic degradation of targeted proteins by reversible covalent PROTACs. | Nature Communications

Fig. 1: Demonstration of catalytic degradation of targeted proteins by reversible covalent PROTACs.

From: Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry

Fig. 1

The premise of this reversible covalent PROTAC design is the weak reactivity (mM Kd) between α-cyano-acrylamide group (the chemical structure shown above) and free thiols. Only when the PROTAC molecule binds to the active site of the targeted protein, the nearby cysteine side chain can react with the α-cyano-acrylamide group to form a stable covalent bond. Once the targeted protein is degraded, the reversible covalent PROTAC can be regenerated.

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