Aziridine-2,3-dicarboxylic acid derivatives as inhibitors of papain

Article abstract of DOI:10.1002/ardp.19963290504

Aziridine-2,3-dicarboxylates and N-acylated derivatives have been evaluated as potential irreversible inhibitors of the cysteine proteinase papain. Dependence of inhibition activity on stereochemistry of the aziridine moiety has been analyzed. Whereas unsubstituted (R,R)- and (S,S)-diethyl aziridine-2,3-dicarboxylates (5) and (2) show no significant difference in inactivation the derivative acylated with BOC-(S)-Phe (BOC-(S)-Phe-(S,S)-Azi) (10) shows a 6 fold higher activity than the diastereomer BOC-(S)-Phe-(R,R)-Azi (11). Analogs acylated with Z- or BOC-(S)-Ala (9, 8) have lower second-order rate constants, indicating binding of the amino acid moiety of the inhibitors to the S2 subsite of the enzyme.