Use of pyridazinediones as extracellular cleavable linkers through reversible cysteine conjugation

Abstract

Herein we report a retro-Michael deconjugation pathway of thiol–pyridazinedione linked protein bioconjugates to provide a novel cleavable linker technology. We demonstrate that the novel pyridazinedione linker does not suffer from off-target modification with blood thiols (e.g., glutathione, human serum albumin (HSA)), which is in sharp contrast to an analogous maleimide linker.