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Published TCIMAIL newest issue No.197
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Dipeptides Degradable by Enzyme in Lysosome
No.183(April 2020)
1, 2, 3, 4, and 5 are dipeptides containing valine (Val)-citrulline (Cit) and p-aminobenzylalcohol (PAB) moieties. It has been reported that Cathepsin B in the lysosome degrades the peptide bond between Cit-PAB.1) Therefore, a drug conjugate bound covalently with carbamate bonds between PAB and the drug can be synthesized by using the dipeptide as a linker. The drug can be then released by hydrolysis after cleavage of the peptide bond between Cit-PAB. Antibody-drug conjugates (ADCs) in which the N-terminus of Val is bound to an antibody have been developed.2)
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
- 2)Effect of Attachment Site on Stability of Cleavable Antibody Drug Conjugates
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