Nickel-Catalyzed Antibody Bioconjugation.
Vlad BacauanuZoe N MerzZhong L HuaSimon B LangPublished in: Journal of the American Chemical Society (2023)
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.
Keyphrases
- drug discovery
- living cells
- room temperature
- small molecule
- ionic liquid
- fluorescence imaging
- fluorescent probe
- single molecule
- reduced graphene oxide
- protein protein
- rheumatoid arthritis
- amino acid
- oxide nanoparticles
- high throughput
- metal organic framework
- nucleic acid
- cancer therapy
- molecularly imprinted
- drug release
- drug delivery
- high resolution