These authors demonstrate that palladium(II) complexes can be used in efficient and highly selective cysteine conjugation reactions that are rapid and robust, and the resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the new bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody–drug conjugates. Previously the use of transition-metal based reactions to modify complex biomolecules has proved problematic due mainly to the need for stringent reaction conditions and the presence of multiple reactive functional groups in peptides.
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