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...

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Veröffentlicht in:Journal of the American Chemical Society 2023-11, Vol.145 (47), p.25842-25849
Hauptverfasser: Bacauanu, Vlad, Merz, Zoe N, Hua, Zhong L, Lang, Simon B
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container_title Journal of the American Chemical Society
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creator Bacauanu, Vlad
Merz, Zoe N
Hua, Zhong L
Lang, Simon B
description 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.
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subjects Antineoplastic Agents - chemistry
Catalysis
Immunoconjugates - chemistry
Nickel
Peptides - chemistry
Proteins - chemistry
title Nickel-Catalyzed Antibody Bioconjugation
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