Trifunctional Dibromomaleimide Reagents Built Around A Lysine Scaffold Deliver Site‐selective Dual‐modality Antibody Conjugation

Abstract

We describe the synthesis and application of a selection of trifunctional reagents for the dual‐modality modification of native, solvent accessible disulfide bonds in trastuzumab. The reagents were developed from the dibromomaleimide (DBM) platform with two orthogonal clickable functional groups built around a lysine core. We also describe the development of an aryl diselenide additive which enables antibody disulfide reduction in 4 minutes and a rapid overall reduction‐bridging‐double click sequence.