Cathepsin B in the lysosome cleaves the peptide bond between Cit-PAB of dipeptide linkers containing valine (Val)-citrulline (Cit) and p-aminobenzylalcohol (PAB). When PAB and a drug are binded covalently with carbamate bonds, the drug can be released by hydrolysis after cleavage of the peptide bond between Cit-PAB. Antibody-drug conjugates (ADCs) has been developed using this mechanism.

Products

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Advantages

• Contain Val-Cit sequence degradable by a lysosome enzyme
• Have superior plasma stability comparable to that of non-cleavable linkers
• Available for manufacturing with several tens gram scale

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References

• 1) 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 activity.
  • G. M. Dubowchik, R. A. Firestone, L. Padilla, D. Willner, S. J. Hofstead, K. Mosure, J. O. Knipe, S. J. Lasch, P. A. Trail, Bioconjugate Chem. 2002, 13, 855.
• 2) A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy
  • Y. Yoneda, S. C. J. Steiniger, K. Čapková, J. M. Mee, Y. Liu, Gunnar, F. Kaufmann, K. D. Janda, Bioorg. Med. Chem. Lett. 2008, 18, 1632.
• 3) Effect of Attachment Site on Stability of Cleavable Antibody Drug Conjugates
  • M. Dorywalska, P. Strop, J. A. Melton-Witt, A. Hasa-Moreno, S. E. Farias, M. G. Casas, K. Delaria, V. Lui, K. Poulsen, C. Loo, S. Krimm, G. Bolton, L. Moine, R. Dushin, T.–T. Tran, S.-H. Liu, M. Rickert, D. Foletti, D. L. Shelton, J. Pons, A. Rajpal, Bioconjugate Chem. 2015, 26, 650.

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Related Product Page

• Well-used Cross-linkers for Antibody-Drug Conjugates (ADC)

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Related Product Category Pages

• Linkers and Crosslinkers
• Bioconjugation
• Drug Delivery Systems (DDS)

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Product Brochure

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