Novel Cell-Permeable Acyloxymethylketone Inhibitors of Asparaginyl Endopeptidase
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| 024 | 7 | 0 | |a 10.1515/BC.2003.136 |2 doi |
| 035 | |a (NATIONALLICENCE)gruyter-10.1515/BC.2003.136 | ||
| 245 | 0 | 0 | |a Novel Cell-Permeable Acyloxymethylketone Inhibitors of Asparaginyl Endopeptidase |h [Elektronische Daten] |c [K. Loak, D. N. Li, B. Manoury, J. Billson, F. Morton, E. Hewitt, C. Watts] |
| 520 | 3 | |a 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. | |
| 540 | |a Copyright © 2003 by Walter de Gruyter GmbH & Co. KG | ||
| 690 | 7 | |a Biochemistry |2 nationallicence | |
| 690 | 7 | |a Molecular biology |2 nationallicence | |
| 690 | 7 | |a Cellular biology |2 nationallicence | |
| 700 | 1 | |a Loak |D K. |4 aut | |
| 700 | 1 | |a Li |D D. N. |4 aut | |
| 700 | 1 | |a Manoury |D B. |4 aut | |
| 700 | 1 | |a Billson |D J. |4 aut | |
| 700 | 1 | |a Morton |D F. |4 aut | |
| 700 | 1 | |a Hewitt |D E. |4 aut | |
| 700 | 1 | |a Watts |D C. |4 aut | |
| 773 | 0 | |t Biological Chemistry |d Walter de Gruyter |g 384/8(2003-08-20), 1239-1246 |x 1431-6730 |q 384:8<1239 |1 2003 |2 384 |o bchm | |
| 856 | 4 | 0 | |u https://doi.org/10.1515/BC.2003.136 |q text/html |z Onlinezugriff via DOI |
| 908 | |D 1 |a research article |2 jats | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1515/BC.2003.136 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Loak |D K. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Li |D D. N. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Manoury |D B. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Billson |D J. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Morton |D F. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hewitt |D E. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Watts |D C. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biological Chemistry |d Walter de Gruyter |g 384/8(2003-08-20), 1239-1246 |x 1431-6730 |q 384:8<1239 |1 2003 |2 384 |o bchm | ||
| 900 | 7 | |b CC0 |u http://creativecommons.org/publicdomain/zero/1.0 |2 nationallicence | |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-gruyter | ||