Disulfide re-bridging reagents for single-payload antibody-drug conjugates†

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.

Abstract

A tetra-reactive disulfide re-bridging reagent, TetraDVP, enables the efficient synthesis of antibody-drug conjugates (ADCs) bearing a single payload.