Investigating a Boronate-Affinity Guided Acylation Reaction for Labelling Native Antibodies.

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 execution of 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-labeled Ab (N 3 -Ab) quantitatively cleaved upon brief exposure to UV light while retaining the original Ab activity. Click reactions enabled precise addition of biotin, fluorophore, and a pharmacological agent to the purified N 3 -Abs. The resulting immunoconjugate showed effective cytotoxicity against targeted cells. Bioorthogonal traceless design and reagentless purification allow for this strategy to be a powerful tool to engineer native antibodies amenable to therapeutic intervention.

• Publication year

  2022

• Venue

  Chemistry

• Publication date

  2022-02-10

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/chem.202104178PMID 35143090
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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