Author/Authors :
Christophe Mellon، نويسنده , , Renée Aspiotis، نويسنده , , Cameron W. Black، نويسنده , , Christopher I. Bayly، نويسنده , , Erich L. Grimm، نويسنده , , André Giroux، نويسنده , , Yongxin Han، نويسنده , , Elise Isabel، نويسنده , , Daniel J. McKay، نويسنده , , Donald W. Nicholson، نويسنده , , Dita M. Rasper، نويسنده , , Anne Sophie Roy ، نويسنده , , John Tam، نويسنده , , Nancy A. Thornberry، نويسنده , , John P. Vaillancourt، نويسنده , , Steven Xanthoudakis، نويسنده , , Robert Zamboni، نويسنده ,
Abstract :
Caspase 3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact in the treatment of several degenerative diseases. The P1 aspartic acid residue is a required element of recognition for this enzyme that was maintained constant along with the adjacent natural valine as the P2 group. The thiobenzylmethylketone warhead on the aspartate was conveniently handled through solid-phase synthesis allowing modification in the P3 region that eventually led to simpler derivatives with increased potency against caspase 3. The key to such an effect is the introduction of hydroxyl group alpha to the P3 carbonyl.
