Nickel-Catalyzed Antibody Bioconjugation

New biocompatible methods for post-translational protein modification are challenging to develop but crucial to create improved chemical probes and optimize next-generation biologic therapies such as antibody-drug conjugates (ADCs). Herein, we describe the bottom-up construction of an aqueous nickel-catalyzed cross-coupling for the chemospecific arylation of cysteine residues on peptides and proteins and its use for the preparation of ADCs. A variety of arene linkages are exemplified, enabling the incorporation of small molecules, probes, and cytotoxic payloads. The utility of this new bioconjugation platform in a drug discovery setting is highlighted by the construction of novel ADCs with target-mediated in vitro cytotoxic activity.

Automated summary

This article describes a new biocompatible method for post-translational protein modification, which is crucial for improving chemical probes and biologic therapies. By utilizing a specific chemical reaction, aromatic compounds can be linked to cysteine residues on peptides and proteins for the preparation of ADCs. The application of this method in drug discovery is highlighted, demonstrating the construction of novel ADCs with target-mediated in vitro cytotoxic activity.