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 [human] 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 and/or N-dichloroamine. N-Monochloropeptides were the main products at higher pH values; at lower pH a 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-formyl-amino 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. [The chlorination process may be important in bactericidal mechanisms of neutrophils.].