Cross-linking of proteins by maillard processes—Model reactions of d-glucose or methylglyoxal with butylamine and guanidine derivatives Original Research Article

Advanced Maillard reaction in proteins leads to formation of covalently cross-linked aggregates the chemical nature of which is largely unknown. From model reactions of methylglyoxal and butylamine with creatine or α-N-acetyl-l-arginine, one main product each was isolated. These two compounds were identified, on the basis of unequivocal spectroscopic evidence, as 2-[(5-butylimino-4-methyl-4,5-dihydro-1H-2-imidazolyl)(methyl)amino]acetic acid and 2-acetylamino-5-[(5-butylimino-4-methyl-4,5-dihydro-1H-2-imidazolyl)amino]pentanoic acid, respectively. Using d-glucose instead of methylglyoxal, two main products each were obtained from reaction with the respective guanidine derivative. The spectroscopic data definitively establish the formation of the diastereoisomeric 2-[(4-butyl-6,7-dihydroxy-4,5,6,7,8,8a-hexahydroimidazo[4,5-b]azepin-2-yl)(methyl)amino]acetic acid from the reaction with creatine, and of the diastereoisomeric 2-acetylamino-5-[(4-butyl-6,7-dihydroxy-4,5,6,7,8,8a-hexahydroimidazo[4,5-b]azepin-2-yl)amino]pentanoic acid from the reaction with α-N-acetyl-l-arginine. All products were isolated in fairly good yield and represent 1:1:1 adducts of the respective reaction partners. Formation of these compounds thus constitutes an efficient reaction pathway for linking primary amines to guanidine derivatives. It seems justified, therefore, to expect cross-linking of proteins by action of reducing carbohydrates to proceed analogously.