Characterization and detection of lysine–arginine cross-links derived from dehydroascorbic acid Original Research Article

Covalently cross-linked proteins are among the major modifications caused by the advanced Maillard reaction. So far, the chemical nature of these aggregates is largely unknown. l-Dehydroascorbic acid (DHA, ), the oxidation product of l-ascorbic acid (vitamin C), is known as a potent glycation agent. Identification is reported for the lysine–arginine cross-links N6-[2-[(4-amino-4-carboxybutyl)amino]-5-(2-hydroxyethyl)-3,5-dihydro-4H-imidazol-4-ylidene]-l-lysine (), N6-[2-[(4-amino-4-carboxybutyl)amino]-5-(1,2-dihydroxyethyl)-3,5-dihydro-4H-imidazol-4-ylidene]-l-lysine (), and N6-[2-[(4-amino-4-carboxybutyl)amino]-5-[(1S,2S)-1,2,3-trihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene]-l-lysine (). The formation pathways could be established starting from dehydroascorbic acid (), the degradation products 1,3,4-trihydroxybutan-2-one (, l-erythrulose), 3,4-dihydroxy-2-oxobutanal (, l-threosone), and l-threo-pentos-2-ulose (, l-xylosone) were proven as precursors of the lysine–arginine cross-links , , and . Products and were synthesized starting from DHA , compound N6-[2-[(4-amino-4-carboxybutyl)amino]-5-[(1S,2R)-1,2,3-trihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene]-l-lysine () via the precursor d-erythro-pentos-2-ulose (). The present study revealed that the modification of lysine and arginine side chains by DHA is a complex process and could involve a number of reactive carbonyl species.