Disease relevance of C02202

• Z-Phe-Phe-CHN2, a specific inhibitor of cathepsin L, significantly inhibited the proteolytic activity present in uterine flushings [1].
• Z-Phe-Phe-CHN2, a selective inhibitor of cathepsin L, at 1, 5, and 10 microM, inhibited bone resorption by rat osteoclasts 50, 85, and 100 per cent and, in chicken osteoclasts, cathepsin L activity was comparably inhibited [2].
• The activities of cathepsin B- and L-like proteinases in homogenised gingival tissue from control and periodontitis patients were measured biochemically using the selective peptide substrate Z-Phe-Arg-AFC and the selective cathepsin L inhibitor Z-Phe-Phe-CHN2 [3].

High impact information on C02202

• The pH optimum for cathepsin B (substrate: Z-Arg-Arg-HNMec) and L (substrate: Z-Phe-Arg-HNMec in the presence of Z-Phe-Phe-CHN2) was approximately pH 6.0 for both glomeruli and renal cortex; while that for cathepsin H (substrate: Arg-HNMec) was approximately 6 [4].
• Under identical conditions Z-Phe-Phe-CHN2 (0.56 microM) completely inhibits cathepsin L but has little effect on cathepsin B. Incubation of glomerular basement membrane (GBM) with purified human kidney cathepsin L resulted in dose-dependent (10-40 nM) GBM degradation [5].
• Cathepsin L exhibited a single band of Mr 27,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, presented a high affinity for the substrate Z-Phe-Arg-NMec, was very unstable at neutral pH, and was inhibited by Z-Phe-Phe-CHN2 [6].
• The stability of cathepsin S at pH 7.5 and the resistance of cathepsin B against inactivation by 0.5 microM Z-Phe-Phe-CHN2 permitted differentiation of these enzyme activities [7].
• Kapp, the second-order rate constant of enzyme inactivation by Z-Phe-Phe-CHN2 with LE as substrate was 31,530 M-1 s-1 or 10(3) higher than its effect on cathepsin B-mediated hydrolysis of ME-Arg-Phe at the Met-Arg site [8].

Anatomical context of C02202

• Culture for 5 days with thiol protease inhibitors such as leupeptin, E-64 or Z-Phe-Phe-CHN2 partially restored the beta-galactosidase activity of fibroblasts from patients, but did not affect the beta-galactosidase activity of fibroblasts from control subjects [9].

Gene context of C02202

• Both were rapidly inhibited by low concentrations of E-64 or leupeptin, but were unaffected by cathepsin-L-specific inhibitor Z-Phe-Phe-CHN2 [10].

References