| Autor: |
Thompson, S. K., Smith, W. W., Zhao, B., Halbert, S. M., Tomaszek, T. A., Tew, D. G., Levy, M. A., Janson, C. A., DAlessio, K. J., McQueney, M. S., Kurdyla, J., Jones, C. S., DesJarlais, R. L., Abdel-Meguid, S. S., Veber, D. F. |
| Zdroj: |
Journal of Medicinal Chemistry; October 8, 1998, Vol. 41 Issue: 21 p3923-3927, 5p |
| Abstrakt: |
Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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