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 |
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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. |
doi_str_mv | 10.1021/jacs.3c10185 |
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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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