Peptide-Directed Attachment of Hydroxylamines to Specific Lysines of IgG Antibodies for Bioconjugations with Acylboronates
Abstract
The role of monoclonal antibodies as vehicles to deliver payloads has evolved as a powerful tool in cancer therapy in recent years. The clinical development of therapeutic antibody conjugates with precise payloads holds great promise for targeted therapeutic interventions. The use of affinity-peptide mediated functionalization of native off-the-shelf antibodies offers an effective approach to selectively modify IgG antibodies with a drug–antibody ratio (DAR) of 2. Here, we report the traceless, peptide-directed attachment of two hydroxylamines to native IgGs followed by chemoselective potassium acyltrifluoroborate (KAT) ligation with quinolinium acyltrifluoroborates (QATs), which provide enhanced ligation rates with hydroxylamines under physiological conditions. By applying KAT ligation to the modified antibodies, conjugation of small molecules, proteins, and oligonucleotides to off-the-shelf IgGs proceeds efficiently, in good yields, and with simultaneous cleavage of the affinity peptide-directing moiety. Show more
Publication status
publishedExternal links
Journal / series
Angewandte Chemie. International EditionVolume
Pages / Article No.
Publisher
Wiley-VCHSubject
Antibodies; Affinity peptide; Conjugation; Antibody-drug conjugate; KAT LigationFunding
ETH-44 17-2 - Rapid reactions for the fluorine-18 labeling of peptides and proteins for use as positron emission tomography (PET) imaging agents (ETHZ)
Related publications and datasets
Is new version of: https://doi.org/10.3929/ethz-b-000651954
More
Show all metadata
ETH Bibliography
yes
Altmetrics