Oxidation of methionine peptides by Fenton systems: the importance of peptide sequence, neighbouring groups and EDTA

Abstract

We investigated the anaerobic oxidation of several Thr- and Met-containing di- and tri-peptides by Fenton systems, (NH₄)₂Fe(SO₄)₂/H₂O₂ and [Fe^II(EDTA)]^2–/H₂O₂, respectively, and compared the respective product patterns with those obtained after oxidation with free radiation chemically generated hydroxyl radicals. The products obtained by the (NH₄)₂Fe(SO₄)₂/H₂O₂ system did not show any significant resemblance to product patterns characteristic for free hydroxyl radicals. In contrast, the [Fe^II(EDTA)]^2–/H₂O₂ system generated a material balance which showed some similarity to the free hydroxyl radical-generated pattern. From a comparison of the relative reactivities of the various functional groups of the peptides with the quantities of products obtained, we conclude that for Thr Met, in particular at pH 6.3, a direct attack of a fraction of reactive oxygen species at the Met sulfur caused the formation of a sulfuranyl radical intermediate. This then underwent intramolecular coupled proton/electron-transfer with the protonated N-terminus to yield nitrogen-centered radical cations. The latter subsequently suffered heterolytic fragmentation of the C_α–C_β bond of Thr to yield acetaldehyde. Such a pathway had previously been characterized for the oxidation of Thr-Met by free HO˙. The occurrence of such intramolecular radical transformation is taken as evidence that neighbouring group effects can operate during metal-catalysed peptide (and possibly protein) oxidation.