In Search of Selective Inhibitors of Cysteine Protease, Cathepsin K

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• 作者：Ewa Wieczerzak ; Piotr Drabik ; Magnus Abrahamson and Anders Grubb
• 关键词：Azapeptide ; cathepsin K ; cysteine protease ; inhibitor ; molecular dynamics
• 刊名：International Journal of Peptide Research and Therapeutics
• 出版年：2005
• 出版时间：September 2005
• 年：2005
• 卷：11
• 期：3
• 页码：203-209
• 全文大小：264 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Animal Anatomy, Morphology and Histology
  Polymer Sciences
  
• 出版者：Springer Netherlands
• ISSN：1573-3904

文摘

Two potential azapeptide inhibitors of cathepsin K were designed and synthesized. To analyze in detail interactions between these azainhibitors and the investigated cysteine protease, molecular dynamics simulations were performed. For the obtained compounds the equilibrium constants for dissociation of inhibitor – enzyme complex, K_i, were determined. The examined azapeptides proved to be not as potent inhibitors of cathepsin K as they were expected to be according to the results of simulations. However, these calculations provide valuable information about probable structures of this type of peptidomimetics in the catalytic pocket of cathepsin K, which could be useful in designing of more selective inhibitors of this cysteine protease.