Kinetics and mechanism of the cleavage of the peptide bond next to asparagine

Abstract

The spontaneous cleavage reaction of the tetra-peptide Piv-Gly Asn-Sar-Gly-NHtBu to the C-terminal dipeptide and N-terminal succinimide dipeptide proceeds through pre-equilibrium deprotonation of the amide group of the asparagine side chain, followed by intramolecular nucleophilic attack of nitrogen on the peptide carbonyl carbonyl carbon atom. General acid-catalyzed breakdown of the intermediate then gives the products. According to this mechanism, the reaction rate strongly increases with pH and buffer concentration.