In Search of Selective Inhibitors of Cysteine Protease,Cathepsin K

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.