The thra¢-membered ring of aziridine-2-carboxylic acid, which is susceptible to alining by nuclcophilcs, has been analyzed as a potential useful handle for the desisn of ~p¢cifi¢ irrevcrsibl~ inhibitors of ¢ysteine proteinases. For this thiol-reactiv¢ amino avid, an imino analogue of proline, a s~ond.order rate constant of 17.07 M-~.s -~ for inactivation of papain was determined. Thus° the aziridine moiety proved to be remarkably more reactive than activated double bonds° ¢.g. N-eth~,lmaleimide, or halides such as,,-iodopropionic acid or chloroaoctie acid. Since it dccs 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 oi" irreversible inhibitors, at least in terms of specificity of the chemical reaction involved in the inactivation process.