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.
Patel
K
K
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Borchardt
R T
RT
D000577:Amides / Q000032:analysis; D000595:Amino Acid Sequence; D001216:Asparagine / Q000032:analysis*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000032:analysis* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000032:analysis* / Q000493:pharmacokinetics; D013696:Temperature
D000577:Amides; D002021:Buffers; D009842:Oligopeptides; D010446:Peptide Fragments; C089005:valyl-tyrosyl-prolyl-asparaginyl-glycyl-alanine; D001216:Asparagine