.OH RADICAL INDUCED DECARBOXYLATION OF METHIONINE-CONTAINING PEPTIDES - INFLUENCE OF PEPTIDE SEQUENCE AND NET CHARGE

The .OH radical induced oxidation of methionine-containing peptides results in significantly different decarboxylation yields upon variation of the location of the methionine unit with respect to the terminal functions (Met-Gly, Met-Glu, Met-Gly-Gly, Gly-Met-Gly, Gly-Met and Gly-Gly-Met), or with the nature of neighbouring amino acids located at the N-terminus of methionine (Ala-Met, beta-Ala-Met, Val-Met, Leu-Met, Ser-Met, Thr-Met, His-Met, gamma-Glu-Met, Pro-Met, Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Met). The CO2 yields measured in gamma-radiolysis vary from 0% (Met-Gly, Met-Glu, Met-Gly-Gly, Gly-Met-Gly, and Pro-Met) to about 80% (gamma-Glu-Met) of the .OH radicals available. Mechanistically, the decarboxylation is considered to proceed via an intramolecular 'outer sphere' electron transfer from the methionine carboxylate function to the oxidized sulphur function > S.+. An additional N-terminal decarboxylation route exists in gamma-Glu-Met which requires assistance by the alpha-positioned free amino group. Both processes compete with deprotonation of > S.+ at the carbon atom alpha-positioned to sulphur. The relative rates of all these competing pathways, and consequently the decarboxylation yields, are shown to depend on (i) the electron inductive properties of substituent groups at the alpha-carbon of the N-terminal amino acid, (ii) the net electric charge of the peptide molecule, and (iii) the distance between the centres of positive charge (-NH3+ and > S.+).