Collect. Czech. Chem. Commun. 1992, 57, 179-187

Linear Tri- and Tetrapeptides Acting as Prodrugs

Evžen Kasafírek, Antonín Šturc and Alena Roubalová

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Tri- and tetrapeptides with C-terminal 1-amino-1-cycloalkanecarboxylic acid of the general formula X-Ala-Y-OR, where X is Ala, Leu, Phe, Ac-Tyr, Gly-Pro, Ac-Leu-Lys or Ac-Leu-Arg, Y is Acb, Acp or Ach, and R is methyl or ethyl, have been prepared. These peptides containing a rationally chosen N-substituent are cleaved with a suitable enzyme (leucinaminopeptidase, alaninaminopeptidase, chymotrypsin, plasmin or kallikrein) in an aqueous medium. The arising C-terminal dipeptide ester undergoes spontaneous cyclization to give biologically active spirocyclic dipeptide. The prepared short peptides exhibit all functional features of prodrugs.