Syndivia and Prof. Jean-Marie Lehn's Group Reveal Novel Conjugation Strategy

STRASBOURG (France) – January 15, 2025 – Syndivia, in collaboration with the group of Prof. Jean-Marie Lehn at the University of Strasbourg, has published new findings on a novel site-selective conjugation strategy leveraging subtle structural differences within the IgG4 antibody subfamily.

Through 3D structural analysis, the study identifies a unique spatial arrangement of lysine residues near hinge-region disulfide bonds in IgG4 — a pattern not observed in IgG1. This structural peculiarity can be exploited to enhance the specificity of bioconjugation reactions, offering a refined approach for the development of homogeneous antibody-drug conjugates (ADCs).

The strategy relies on a dynamically reversible reagent scaffold, capable of interacting transiently with lysine residues across the antibody. Covalent attachment occurs only when a proximal reduced disulfide bond is present, effectively using lysines as transient “carriers” to target defined sites. This selective mechanism significantly narrows the distribution of conjugation outcomes.

🔗 Read the full publication: https://pubs.acs.org/doi/abs/10.1021/jacs.4c15421