Long-Term Stabilization of Maleimide–Thiol Conjugates

Michael-addition of a thiol to a maleimide is commonly used for bioconjugation of drugs to macromolecules. Indeed, both current FDA-approved antibody–drug conjugates—Brentuximab vedotin and Trastuzumab emtansine—and one approved PEGylated conjugate—Cimzia—contain a thiol–maleimide adduct. However, the ultimate in vivo fate of such adducts is to undergo disruptive cleavage by thiol exchange or stabilizing ring opening. Therapeutic efficacy of a...