Disulfide re-bridging reagents for single-payload antibody-drug conjugates
Thomas A. King, Stephen J. Walsh, Mia Kapun, Thomas Wharton, Soňa Krajčovičová, Melanie S. Glossop, David R. Spring
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.
Topics & Concepts
Bridging (networking)ConjugateReagentDisulfide bondDrugChemistryCombinatorial chemistryAntibody-drug conjugatePayload (computing)AntibodyComputer scienceMonoclonal antibodyPharmacologyMedicineBiochemistryOrganic chemistryImmunologyMathematicsMathematical analysisComputer networkNetwork packetMonoclonal and Polyclonal Antibodies ResearchHER2/EGFR in Cancer ResearchPeptidase Inhibition and Analysis