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Updated: Jul 21, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Disulfide re-bridging reagents for single-payload antibody-drug conjugates
Thomas A King1, Stephen J Walsh1, Mia Kapun1
1Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. spring@ch.cam.ac.uk.
Abstract:
Numerous antibody-drug conjugate (ADC) linker technologies exist for the synthesis of ADCs with drug-to-antibody ratios (DARs) being an even integer (typically 2, 4 or 8). However, ADCs with odd-integer DARs are significantly harder to synthesise. Here, we report the synthesis of ADCs loaded with a single warhead, using TetraDVP linkers which simultaneously re-bridge all four interchain disulfides of an IgG1 antibody.
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