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Cysteine-To-Lysine Transfer Antibody Fragment Conjugation

submitted on 15.07.2019, 12:49 and posted on 16.07.2019, 16:27 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.


EPSRC (EP/R034621/1)


Email Address of Submitting Author


University College London


United Kingdom

ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no competing financial interests.


Read the published paper

in Chemical Science