˙OH radical induced decarboxylation of methionine-containing peptides. Influence of peptide sequence and net charge

Abstract

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, β-Ala-Met, Val-Met, Leu–Met, Ser–Met, Thr–Met, His–Met, γ-Glu–Met, Pro–Met, Gly–Gly–Phe–Met and Tyr–Gly–Gly–Phe–Met). The CO₂ yields measured in γ-radiolysis vary from 0%(Met–Gly, Met–Glu, Met–Gly–Gly, Gly–Met–Gly, and Pro–Met) to about 80%(γ–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 γ-Glu–Met which requires assistance by the α-positioned free amino group. Both processes compete with deprotonation ofS˙⁺ at the carbon atom α-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 α-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˙⁺).