A modular and convergent "Stick and Click" conjugation platform enables fast antibody conjugate library synthesis

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Livingstone, Connor and Nicolle, Simon and Jones, Gavin and Jamieson, Craig (2026) A modular and convergent "Stick and Click" conjugation platform enables fast antibody conjugate library synthesis. Bioconjugate Chemistry, 37 (1). pp. 40-51. ISSN 1520-4812 (https://doi.org/10.1021/acs.bioconjchem.5c00461)

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Abstract

The preparation of antibody drug conjugates (ADC) most often relies on a linear sequence to elaborate the small molecule component, followed by a final bioconjugation step to attach it to its immunoglobulin partner. This linear and iterative approach is incompatible with expedient parallel synthesis and process automation. Here, we describe the design and implementation of a general modular platform for the assembly of ADCs that enables facile variation in the nature of the payload, the linker composition, and the type of bioconjugation technique used. A library of antibody conjugates bringing together several different antibodies and payloads was prepared in a convergent fashion using a range of conjugation methods, as well as cleavable or noncleavable linker technology. Aside from offering a direct comparison of different conjugation method performances, this approach enables a more targeted optimization strategy of conjugate properties by deconvoluting bioconjugation and payload attachment.

ORCID iDs

Livingstone, Connor, Nicolle, Simon, Jones, Gavin and Jamieson, Craig ORCID logoORCID: https://orcid.org/0000-0002-6567-8272;
CORE (COnnecting REpositories)