The Z-VAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone) is a cell-permeant pan caspase inhibitor that irreversibly binds to the catalytic site of caspase proteases and can inhibit induction of apoptosis. Apoptosis is a physiological form of cell death, which plays important role in embrogenesis, cellular homoestasis, tisue atropy, and removal damaged and mutated cells.Caspases, which act act as molecular chainsaw are the central components of apoptosis response. Caspases are cysteine proteases that cleave after aspartate residue in their substrates. At least 7 of 14 known mammalian caspases have important role in apoptosis. For inhibition of apoptosis, Z-VAD-FMK should be added at the same time that apoptosis is induced. This Z-VAD-FMK peptide is O-methylated in the P1 position on aspartic acid, providing enhanced stability and increased cell permeability. The suggested concentration for use in the anti-Fas mAb-treated Jurkat cell culture model system is 20μM. |