Intracellular oxidation of dipeptides. Very fast halogenation of the amino-terminal residue

Abstract

Peptides undergo a very fast halogenation reaction with aqueous halogens. The process takes place via aliphatic electrophilic substitution with bimolecular rate constants of ca. 107 M−1 s−1. The products formed are N-halo-peptides, i.e., the halogenation process takes place on the nitrogen atom at the amino-terminal moiety of the amino acid residue. At ratios [halogenating agent]/[dipeptide] ≤ 1, no analytical or kinetic evidence has been found of halogenation on the peptide bond or on the oxygen atom of the carboxy-terminal residue. The intracellular oxidation of peptides to N-halo-peptides proceeds by an in vivo mechanism to reduce the oxidative stress caused by intracellular oxidants.