N-(2-Oxoacyl)amino acids and nitriles as final products of dipeptide chlorination mediated by the myeloperoxidase/H2O2/Cl- system

Abstract

The chlorination of dipeptides by the myeloperoxidase/H2O2/Cl- system takes place at the N-terminal amino group, whereas no chlorination of the amide nitrogen of the peptide bond can be observed. The N-terminal amino group is chlorinated to N-monochloroamine or/and N-dichloroamine. N-Monochloropeptides were the main products at higher pH values, at lower pH at mixture of N-monochloropeptides and N-dichloropeptides was formed owing to the dismutation of N-monochloroamine to N-dichloroamine. N-Monochloropeptides decompose, yielding NH3 and the corresponding N-(2-oxoacyl)amino acids. N-Dichlorodipeptides decompose faster but to nitriles and the free C-terminal amino acids. N-Dichloroglycyl-amino acid decomposes through a relatively stable intermediate (cyano-formylamino acid) to hydrogen cyanide, cyanogen chloride and the free C-terminal amino acid. Insulin chlorination also yields N-terminal glycyl and phenylalanyl N-monochloro derivatives, which deaminate to glyoxylyl and phenylpyruvyl residues.