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Aziridine‐2‐carboxylic acid A reactive amino acid unit for a new class of cysteine proteinase inhibitors
Author(s) -
Morodor L.,
Musiol H.-J.,
Scharf R.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80098-2
Subject(s) - aziridine , chemistry , chloroacetic acid , cysteine , alkylation , moiety , carboxylic acid , nucleophile , amino acid , thiol , stereochemistry , maleic acid , papain , histidine , enzyme , biochemistry , organic chemistry , ring (chemistry) , catalysis , polymer , copolymer
The three‐membered ring of aziridine‐2‐carboxylic acid, which is susceptible to opening by nucleophiles, has been analyzed as a potential useful handle for the design of specific irreversible inhibitors of cysteine proteinases. For this thiol‐reactive amino acid, an imino analogue of proline, a second‐order rate constant of 17.07 M −1 s −1 for inactivation of papain was determined. Thus, the aziridine moiety proved to be remarkably more reactive than activated double bonds, e.g. N ‐ethylmaleimide, or halides such as α‐iodopropionic acid or chloroacetic acid. Since it does not alkylate histidine under conditions in which quantitative alkylation occurs with N ‐ethyl‐maleimide, it could represent an interesting reactive amino acid unit for the synthesis of a new class of irreversible inhibitors, at least in terms of specificity of the chemical reaction involved in the inactivation process.