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Aziridine‐2,3‐dicarboxylic Acid Derivatives as Inhibitors of Papain
Author(s) -
Schirmeister Tanja
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290504
Subject(s) - aziridine , chemistry , moiety , papain , stereochemistry , diastereomer , dicarboxylic acid , cysteine , amino acid , enzyme , organic chemistry , biochemistry , ring (chemistry)
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.