CHEMICAL PATHWAYS OF PEPTIDE DEGRADATION .5. ASCORBIC-ACID PROMOTES RATHER THAN INHIBITS THE OXIDATION OF METHIONINE TO METHIONINE SULFOXIDE IN SMALL MODEL PEPTIDES

The effect of primary structure and external conditions on the oxidati on of methionine to methionine sulfoxide by the ascorbate/Fe3+ system was studied in small model peptides. Degradation kinetics and yield of sulfoxide formation were dependent on the concentration of ascorbate and H+, with a maximum rate observed at pH 6-7. Phosphate buffer signi ficantly accelerated the peptide degradation compared to Tris, HEPES, and MOPS buffers; however, the formation of sulfoxide was low. The oxi dation could not be inhibited by the addition of EDTA. Other side prod ucts besides sulfoxide were observed, indicating the existence of vari ous other pathways. The influence of methionine location at the C term inus, at the N terminus, and in the middle of the sequence was investi gated. The presence of histidine in the sequence markedly increased th e degradation rate as well as the sulfoxide production. The histidine catalysis of methionine oxidation occurred intramolecularly with a max imum enhancement of the oxidation rate and sulfoxide production when o ne residue was placed between the histidine and the methionine residue .