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Cysteine-To-Lysine Transfer Antibody Fragment Conjugation

preprint
submitted on 15.07.2019 and posted on 16.07.2019 by Nafsika Forte, Irene Benni, Kersti Karu, Vijay Chudasama, James R. Baker
The modification of lysine residues with acylating agents has represented a ubiquitous approach to the construction of antibody conjugates, with the resulting amide bonds being robustly stable and clinically validated. However, the conjugates are highly heterogeneous, due to the presence of numerous lysines on the surface of the protein, and greater control of the sites of conjugation are keenly sought. Here we present a novel approach to achieve the targeted modification of lysines distal to an antibody fragment’s binding site, using a disulfide bond as a temporary ‘hook’ to deliver the acylating agent. This cysteine-to-lysine transfer (CLT) methodology offers greatly improved homogeneity of lysine conjugates, whilst retaining the advantages offered by the formation of amide linkages.

Funding

EPSRC (EP/R034621/1)

History

Email Address of Submitting Author

j.r.baker@ucl.ac.uk

Institution

University College London

Country

United Kingdom

ORCID For Submitting Author

0000-0002-7223-2279

Declaration of Conflict of Interest

The authors declare no competing financial interests.

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