| Autor: |
Ward, Y. D., Thomson, D. S., Frye, L. L., Cywin, C. L., Morwick, T., Emmanuel, M. J., Zindell, R., McNeil, D., Bekkali, Y., Giradot, M., Hrapchak, M., DeTuri, M., Crane, K., White, D., Pav, S., Wang, Y., Hao, M.-H., Grygon, C. A., Labadia, M. E., Freeman, D. M., Davidson, W., Hopkins, J. L., Brown, M. L., Spero, D. M. |
| Zdroj: |
Journal of Medicinal Chemistry; December 2002, Vol. 45 Issue: 25 p5471-5482, 12p |
| Abstrakt: |
The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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