DiPODS: A Reagent for Site-Specific Bioconjugation via the Irreversible Rebridging of Disulfide Linkages

Chemoselective reactions with thiols have long held promise for the site-specific bioconjugation of antibodies and antibody fragments. Yet bifunctional probes bearing monovalent maleimides—long the “gold standard” for thiol-based ligations—are hampered by two intrinsic issues: the in vivo instability of the maleimide–thiol bond and the need to permanently disrupt disulfide linkages in order to facilitate bioconjugation. Herein, we present the...