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Peptidyl epoxides were designed as selective pseudo-mechanism-based inactivators of cysteine proteases. Both threo- and erythro-peptidyl epoxides were synthesized and tested as potential inactivators of serine proteases (chymotrypsin, subtilisin, and elastase) and of cysteine proteases (papain, cathepsin B, and clostripain). Four tripeptidyl epoxides (Cbz-Gly-Leu-Phe-epoxide, Cbz-Ala-Ala-Phe-epoxide, Cbz-Gly-Leu-Ala-epoxide, and Cbz-Ala-Ala-Ala-epoxide), bearing amino acid sequences similar to those of good substrates or known inhibitors of the serine proteases, were tested in this study. Neither the threo- nor the erythro-peptidyl epoxides exhibited any inhibitory activity toward the serine proteases, even at high concentration and long incubation time. Nor did the threo-peptidyl epoxides inhibit the cysteine proteases. On the other hand, the erythro-peptidyl epoxides were time- and concentration-dependent inactivators of the cysteine proteases. Furthermore, stereoselectivity toward the natural l-amino acid at the P1 position was also exhibited upon inhibition of papain. In order to demonstrate selectivity within the cysteine protease family, two other erythro-peptidyl epoxides (Cbz-Phe-Ala-epoxide and Cbz-Phe-O-Bn-Thr-epoxide) were synthesized and tested as inhibitors of the three cysteine proteases. These new peptidyl epoxides exhibited selective inactivation of cysteine proteases, with second-order rate constants (k i/K i) ranging over 4 orders of magnitude (0.04−330 M-1 s-1). Thus, this new family of highly selective cysteine protease inhibitors offers mechanistic implications and may have useful applications.

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The preparation of modified, catalytically active, functional carbon electrodes and their application to the electrochemical reduction of trinitrotoluene (TNT) is reported. Modification of the electrodes is performed with composites of nanometer‐sized, mesoporous titanium dioxide, which acts as a support containing inserted/deposited nanoparticles of ruthenium, platinum, or gold. These composites are prepared by a novel sonochemical synthesis using simple and low‐cost precursors. Cyclic voltammetry shows that 2,4,6‐trinitrotoluene can be reduced on thus‐modified carbon‐paper electrodes at potentials of around –0.5 V (vs. Ag/AgCl/Cl–) in aqueous solutions. Unexpectedly, carbon‐paper electrodes modified with the TiO2/nano‐Pt composites demonstrate a remarkable electrochemical activity toward the reduction of trinitrotoluene. A significant finding is that the two electrode processes—the reduction of TNT and of oxygen—are quite well separated in potential on the modified carbon‐paper electrodes because of selective electrochemical activity of the TiO2/nano‐Pt and TiO2/nano‐Au composites. TiO2/nano‐Ru composites are found to be much less electrochemically active for the detection of TNT compared to the previous two. It was also established that the titanium dioxide support of TiO2/nano‐Pt composites plays a specific role for facilitating the TNT‐ and oxygen‐reduction processes.

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