Inactivation of cellular caspases by peptide-derived tryptophan and tyrosine peroxides

AbstractPeroxides generated on peptides and proteins within cells, as a result of radical attack or reaction with singlet oxygen, are longer-lived than H2O2 due to their poor removal by protective enzymes. These peroxides readily oxidize cysteine residues and can inactivate thiol-dependent enzymes. We show here that Trp- and Tyr-derived peptide peroxides, generated by singlet oxygen, inhibit caspase activity in the lysates of apoptotic Jurkat cells. N-Ac-Trp-OMe peroxide was the most effective inhibitor, and was 30-fold more effective than H2O2 under identical conditions. As such, protein peroxides could modulate the progression of apoptosis in cells in which they are generated