Aziridine‐2,3‐dicarboxylic Acid Derivatives as Inhibitors of Papain

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 stereo‐chemistry 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.