OXIDATION OF METHIONINE PEPTIDES BY FENTON SYSTEMS - THE IMPORTANCE OF PEPTIDE SEQUENCE, NEIGHBORING GROUPS AND EDTA

We investigated the anaerobic oxidation of several Thr- and Met-contai ning di- and tri-peptides by Fenton systems, (NH4)(2)Fe(SO4)(2)/H2O2 a nd [Fe-II(EDTA)](2-)/H2O2, respectively, and compared the respective p roduct patterns with those obtained after oxidation with free radiatio n chemically generated hydroxyl radicals. The products obtained by the (NH4)(2)Fe(SO4)/H2O2 system did not show any significant resemblance to product patterns characteristic for free hydroxyl radicals. In cont rast, the [Fe-II(EDTA)](2-)/H2O2 system generated a material balance w hich showed some similarity to the free hydroxyl radical-generated pat tern, From a comparison of the relative reactivities of the various fu nctional groups of the peptides with the quantities of products obtain ed, we conclude that for Thr-Met, in particular at pH 6.3, a direct at tack of a fraction of reactive oxygen species at the Met sulfur caused the formation of a sulfuranyl radical intermediate. This then underwe nt intramolecular coupled proton/electron-transfer with the protonated N-terminus to yield nitrogen-centered radical cations. The latter sub sequently suffered heterolytic fragmentation of the C-alpha-C-beta bon d of Thr to yield acetaldehyde. Such a pathway had previously been cha racterized 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.