DECARBOXYLATION MECHANISM OF THE N-TERMINAL GLUTAMYL MOIETY IN GAMMA-GLUTAMIC ACID AND METHIONINE CONTAINING PEPTIDES

The reaction of hydroxyl radicals with gamma-glutamyl-methionine and g amma-glutamyl-glycyl-methionyl-glycine at neutral pH results in simila r N-terminal decarboxylation efficiency. The underlying mechanism invo lves an intramolecular proton transfer from the protonated N-terminal amino group of the glutamyl moiety to an initially formed hydroxy sulp huranyl radical at the methionine residue. This process leads to the f ormation of a three-electron bonded [> S therefore NH2](+)-peptide int ermediate subsequently decomposing into CO2 and an alpha-amino radical of the structure H2N-CH.-CH2-CH2-C(=O)-NH-peptide. This radical has b een identified via reduction of a moderately good electron acceptor su ch as p-nitroacetophenone (PNAP). The arrangement within a sterically favourable 5-membered ring, as observed with methionine, is not a nece ssary prerequisite for the formation of [> S therefore NH2](+)-type in termediate. Mechanistically, the formation of CO, and an a amino radic al suggests the occurrence of an intramolecular electron transfer from the carboxylate group to the electron-deficient center at the nitroge n within the S therefore N-bond followed by homolytic bond breakage of the carbon-carboxylate bond. The decarboxylation benefits in particul ar from stabilization of the arising carbon-centered radical by a free lone pair from the alpha-amino group. This process seems to occur wel l in larger peptide structures provided they contain an N-terminal car boxyl group alpha to an amino function and they are flexible enough to allow the protonated amino function to interact with the hydroxyl sul phuranyl radical at the methionine residue.