Author/Authors :
Elise Isabel، نويسنده , , W. Cameron Black، نويسنده , , Christopher I. Bayly، نويسنده , , Erich L. Grimm، نويسنده , , Marc K. Janes، نويسنده , , Daniel J. McKay، نويسنده , , Donald W. Nicholson، نويسنده , , Dita M. Rasper، نويسنده , , Johanne Renaud، 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. Since P1 aspartic acid is a required element of recognition for this enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was identified to be an inhibitor of caspase-3. Substitution at the 5-position of the pyridine ring and conversion of the aldehyde to ketones led to a series of potent inhibitors of caspase-3.
