Mc-Val-Cit-PAB is a peptide linker molecule used in the synthesis of antibody-drug conjugates (ADCs).1 It contains a maleimidocaproyl (Mc) group that can be conjugated to an antibody and a p-aminobenzyl (PAB) spacer that allows the peptide to be linked to active compounds, such as anticancer agents. Mc-Val-Cit-PAB is cleaved in vivo by cathepsin B, a protease highly expressed in cancer cells, which confers specificity of the ADC to cancer cells. Upon cleavage by cathepsin B, the active compound is released at the target site. Mc-Val-Cit-PAB has been used in the synthesis of an ADC containing the tubulin polymerization inhibitor KGP05. It has also been used as a precursor in the synthesis of Mc-Val-Cit-PABC-PNP .2
1.Mondal, D., Ford, J., and Pinney, K.G.Improved methodology for the synthesis of a cathepsin B cleavable dipeptide linker, widely used in antibody-drug conjugate researchTetrahedron Lett.59(40)3594-3599(2018) 2.Dubowchik, G.M., Firestone, R.A., Padilla, L., et al.Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: Model studies of enzymatic drug release and antigen-specific in vitro anticancer activityBioconjug. Chem.13(4)855-869(2002)