Use of Pyridazinediones as Extracellular Cleavable Linkers Through Reversible Cysteine Conjugation

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.