Chemical pathways of peptide degradation. II. Kinetics of deamidation of an asparaginyl residue in a model hexapeptide.

Deamidation of Asn residues is a major chemical pathway of degradation of peptides and proteins. To understand better the external factors that influence deamidation, we studied the degradation of the hexapeptide Val-Tyr-Pro-Asn-Gly-Ala, a fragment of adrenocorticotropic hormone, by HPLC. The deamidation of this model peptide showed marked dependence on pH, temperature, and buffer composition. In the pH range 5 to 12, the peptide deamidated exclusively via a cyclic imide intermediate with the formation of both the Asp- and the isoAsp-hexapeptides. Buffer catalysis was also observed in the pH range of 7 to 11. However, at acidic pH's, the pathway of deamidation involved direct hydrolysis of the amide side chain of Asn residue to produce only the Asp-hexapeptide.