Dichloro Butenediamides as Irreversible Site?Selective Protein Conjugation Reagent

نویسندگان

چکیده

We describe maleic-acid derivatives as robust cysteine-selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide amido-ester proved be efficient protein-labelling species a common mechanism in which spontaneous cyclization occurs upon addition cysteine. Introduction of chlorine atoms their structures triggers ring hydrolysis or further conjugation adjacent residues, results conjugates that are completely resistant retro-Michael reactions the presence biological thiols human plasma. By controlling microenvironment reactive site, we can control selectivity towards hydrolytic pathway, forming homogeneous conjugates. The method is applicable several scaffolds enables different payloads. synthetic accessibility these mild conditions required fast complete together make this strategy an important alternative maleimides bioconjugation.

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ژورنال

عنوان ژورنال: Angewandte Chemie

سال: 2021

ISSN: ['1521-3773', '1433-7851', '0570-0833']

DOI: https://doi.org/10.1002/ange.202108791