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The excellent molecular recognition capabilities of monoclonal antibodies (mAbs) have opened up exciting opportunities for biotherapeutic discovery. Taking advantage of the full potential of this tool necessitates affinity ligands capable of conjugating directly with small molecules to a defined degree of biorthogonality, especially when modifying natural Abs. Herein, a bioorthogonal boronate‐affinity‐based Ab ligand featuring a 4‐(dimethylamino)pyridine and an S‐aryl thioester to label full‐length Abs is reported. The photoactivatable linker in the acyl donor facilitated purification of azide‐labelled Ab (N3‐Ab) was quantitatively cleaved upon brief exposure to UV light while retaining the original Ab activity. Click reactions enabled the precise addition of biotin, a fluorophore, and a pharmacological agent to the purified N3‐Abs. The resulting immunoconjugate showed selectivity against targeted cells. Bioorthogonal traceless design and reagentless purification allow this strategy to be a powerful tool to engineer native antibodies amenable to therapeutic intervention. [ABSTRACT FROM AUTHOR]

Cover Feature: Investigating a Boronate-Affinity-Guided Acylation Reaction for Labelling Native Antibodies (Chem. Eur. J. 17/2022) Antibodies, antibody-drug conjugates, boronate affinity, boronic acid, protein modifications Keywords: antibodies; antibody-drug conjugates; boronate affinity; boronic acid; protein modifications EN antibodies antibody-drug conjugates boronate affinity boronic acid protein modifications 1 1 1 03/24/22 20220322 NES 220322 B A boronic acid based b biorthogonal probe in combination with an acyl donor has been introduced that enables site-specific incorporation of azide group at the Ser and Tyr residues of nonengineered full-length antibody. [Extracted from the article]