caa a22 4500 378855972 CHVBK 20180305123335.0 cr unu---uuuuu 161128e20031225xx s 000 0 eng 10.1515/BC.2003.179 doi (NATIONALLICENCE)gruyter-10.1515/BC.2003.179 Aza-Peptide Epoxides: Potent and Selective Inhibitors of Schistosoma mansoni and Pig Kidney Legumains (Asparaginyl Endopeptidases) [Elektronische Daten] [K. E. James, M. G. Götz, C. R. Caffrey, E. Hansell, W. Carter, A. J. Barrett, J. H. McKerrow, J. C. Powers] Aza-peptide epoxides are a new class of irreversible cysteine protease inhibitors. Derivatives containing a P1 aza-asparagine residue are specific for Schistosoma mansoni and pig kidney legumains, which are clan CD cysteine proteases. The inhibitors have secondorder rate constants of up to 104 M-1s -1 with pig kidney legumain and IC50 values as low as 45 nM with S. mansoni legumain. The most potent epoxides contain an ester moiety with S,S stereochemistry attached to the epoxide. Interestingly, amide and amino acid derivatives of the epoxysuccinate moiety were not inhibitors of legumain, while disubstituted amide derivatives are quite potent. The inhibitors have little or no inhibitory activity with other proteases such as caspases, chymotrypsin, papain, cathepsin B, granzyme B, and various aspartyl proteases. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence James K. E. aut Götz M. G. aut Caffrey C. R. aut Hansell E. aut Carter W. aut Barrett A. J. aut McKerrow J. H. aut Powers J. C. aut Biological Chemistry Walter de Gruyter 384/12(2003-12-25), 1613-1618 1431-6730 384:12<1613 2003 384 bchm https://doi.org/10.1515/BC.2003.179 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2003.179 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- James K. E. aut NATIONALLICENCE 700 1- Götz M. G. aut NATIONALLICENCE 700 1- Caffrey C. R. aut NATIONALLICENCE 700 1- Hansell E. aut NATIONALLICENCE 700 1- Carter W. aut NATIONALLICENCE 700 1- Barrett A. J. aut NATIONALLICENCE 700 1- McKerrow J. H. aut NATIONALLICENCE 700 1- Powers J. C. aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 384/12(2003-12-25), 1613-1618 1431-6730 384:12<1613 2003 384 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter