caa a22 4500 378853104 CHVBK 20180305123328.0 cr unu---uuuuu 161128e20030820xx s 000 0 eng 10.1515/BC.2003.136 doi (NATIONALLICENCE)gruyter-10.1515/BC.2003.136 Novel Cell-Permeable Acyloxymethylketone Inhibitors of Asparaginyl Endopeptidase [Elektronische Daten] [K. Loak, D. N. Li, B. Manoury, J. Billson, F. Morton, E. Hewitt, C. Watts] Mammalian asparaginyl endopeptidase (AEP) or legumain is a recently identified lysosomal cysteine protease belonging to clan CD. To date it has been shown to be involved in antigen presentation within class II MHC positive cells and in pro-protein processing. Further elucidation of the biological functions of the enzyme will require potent and selective inhibitors and thus we describe here new acyloxymethylketone inhibitors of AEP. The most potent of the series is 2,6-dimethylbenzoic acid 3-benzyloxycarbonylamino-4-carbamoyl-2-oxobutyl ester (MV026630) with a k(obs)/ value of 1.09 exp5 M[-1] s[-1]. At low M concentrations this compound is able to enter living cells and irreversibly inactivate AEP. We show that this results in inhibition of AEP autoactivation and in perturbation of the processing and presentation of T cell epitopes from both tetanus toxin and myelin basic protein. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence Loak K. aut Li D. N. aut Manoury B. aut Billson J. aut Morton F. aut Hewitt E. aut Watts C. aut Biological Chemistry Walter de Gruyter 384/8(2003-08-20), 1239-1246 1431-6730 384:8<1239 2003 384 bchm https://doi.org/10.1515/BC.2003.136 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2003.136 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Loak K. aut NATIONALLICENCE 700 1- Li D. N. aut NATIONALLICENCE 700 1- Manoury B. aut NATIONALLICENCE 700 1- Billson J. aut NATIONALLICENCE 700 1- Morton F. aut NATIONALLICENCE 700 1- Hewitt E. aut NATIONALLICENCE 700 1- Watts C. aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 384/8(2003-08-20), 1239-1246 1431-6730 384:8<1239 2003 384 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter