Chemical pathways of peptide degradation. V. 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 oxidation 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 significantly accelerated the peptide degradation compared to Tris, HEPES, and MOPS buffers; however, the formation of sulfoxide was low. The oxidation could not be inhibited by the addition of EDTA. Other side products besides sulfoxide were observed, indicating the existence of various other pathways. The influence of methionine location at the C terminus, at the N terminus, and in the middle of the sequence was investigated. The presence of histidine in the sequence markedly increased the degradation rate as well as the sulfoxide production. The histidine catalysis of methionine oxidation occurred intramolecularly with a maximum enhancement of the oxidation rate and sulfoxide production when one residue was placed between the histidine and the methionine residue.
Li
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Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Schöneich
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C
Wilson
G S
GS
Borchardt
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RT
D000595:Amino Acid Sequence; D001205:Ascorbic Acid / Q000737:chemistry*; D002021:Buffers; D002712:Chlorides; D004492:Edetic Acid; D005290:Ferric Compounds / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008715:Methionine / Q000031:analogs & derivatives* / Q000737:chemistry*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D013696:Temperature
D002021:Buffers; D002712:Chlorides; D005290:Ferric Compounds; D010455:Peptides; D006639:Histidine; D004492:Edetic Acid; D008715:Methionine; D001205:Ascorbic Acid; C024555:ferric chloride; C013111:methionine sulfoxide