Peptide-Directed Attachment of Hydroxylamines to Specific Lysines of IgG Antibodies for Bioconjugations with Acylboronates
OPEN ACCESS
Loading...
Author / Producer
Date
2023-02-24
Publication Type
Working Paper
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
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 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.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
Pages / Article No.
Publisher
Cambridge University Press
Event
Edition / version
Version 1
Methods
Software
Geographic location
Date collected
Date created
Subject
Antibodies; Affinity peptide; Conjugation; Antibody-drug conjugate; KAT ligation
Organisational unit
03914 - deMello, Andrew / deMello, Andrew
Notes
Funding
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 previous version of: