IRON-THIOLATE INDUCED OXIDATION OF METHIONINE TO METHIONINE SULFOXIDEIN SMALL MODEL PEPTIDES - INTRAMOLECULAR CATALYSIS BY HISTIDINE

Peptides containing either glycine and methionine, or glycine, methion ine and histidine at various locations were oxidized by the dithiothre itol/ferric chloride system in phosphate buffer. The yields of peptide degradation and sulfoxide formation were measured as a function of pe ptide 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 presen t within the same peptide sequence, and particularly when methionine w as located at the C-terminus of the peptide. Added superoxide dismutas e, catalase, and methanol did neither promote nor inhibit both the deg radation of peptide and the formation of sulfoxide excluding free supe roxide, hydrogen peroxide, and hydroxyl radicals as responsible reacti ve 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 methi onine sulfoxide. The first might be a metal-bound peroxide or peroxyl species which converts into a metal-bound or `complexed' hydroxyl radi cal.