Iron-thiolate induced oxidation of methionine to methionine sulfoxide in small model peptides. Intramolecular catalysis by histidine.

Peptides containing either glycine and methionine, or glycine, methionine and histidine at various locations were oxidized by the dithiothreitol/ferric chloride system in phosphate buffer. The yields of peptide degradation and sulfoxide formation were measured as a function of peptide sequence and pH. In general little change of the final yields of peptide degradation is observed whereas the final yields of sulfoxide formation progressively decrease on going from pH 6.0 to 8.0. The pH profiles vary with the structure of the respective peptide. Efficient sulfoxide formation occurred when histidine and methionine were present within the same peptides sequence, and particularly when methionine was located at the C-terminus of the peptide. Added superoxide dismutase, catalase, and methanol did neither promote nor inhibit both the degradation of peptide and the formation of sulfoxide excluding free superoxide, hydrogen peroxide, and hydroxyl radicals as responsible reactive oxygen species. The observations are rationalized by invoking a pH-dependent conversion of an efficiently sulfoxide yielding oxidant into another oxidant which still degrades peptides but does not form methionine sulfoxide. The first might be a metal-bound peroxide or peroxyl species which converts into a metal-bound or 'complexed' hydroxyl radical.