Mal-amido-PEG2-Val-Cit-PAB-PNP is a cleavable ADC linker which contains a maleimide, a hydrophilic PEG spacer, a valine-citrulline (Val-Cit) dipeptide, a para-aminobenzyl (PAB) spacer and a para-nitrophenyl (PNP) carbonate group. Maleimide is a thiol-specific covalent linker which is used to label cysteine residues in proteins while the PNP carbonate acts as a highly activated leaving group which may be used to react with amines. The use of cleavable linkers in the development of ADCs allows a medicinal chemist to decide the point where the drug payload is released to the cell. Val-Cit-PAB linkers are cleaved by cytoplasmic peptidases.
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