Inhibitory activities of E-64 derivatives on papain.

In order to investigate the active site of inhibition of E–64 against papain, the constituents of E-64 and their derivatives were synthesized and their activities on papain were assayed. It was consequently found trans-epoxysuccinic acid was essential for the activity. The difference of its optical activity gave no influence on the activity, but cis-form had no activity. Moreover, the structure-activity relationship of a series of the esters of trans-epoxysuccinic acid was also discussed. From these results, it was suggested that both epoxide and carbonyl group are important in the manifestation of the inhibitory action.