title: Factors affecting cleavage at aspartic residues in model decapeptides.
abstract: The aqueous stability of four decapeptides was investigated in an acetate buffer at different pHs (4.0-5.5) and temperatures (25, 40, and 60 degrees C). The four decapeptides share the following common sequence-Tyr-Ala-Arg-Asp-Aaa-Pro-Leu-Gly-Tyr-Thr, where Aaa represents Gln, Pro, Lys, or Leu. The major degradation pathway was found to be the cleavage at Asp-Aaa. The degradation process fits well the first-order kinetics. The cleavage of the decapeptide containing Asp-Pro was faster than that of other three decapeptides. A strong pH dependence of cleavage was observed for all decapeptides, especially when pH was <5. Three out of four decapeptides showed a clear Arrhenius temperature dependency whereas Asp-Pro-containing peptide did not.
authors.affiliation: Pharmaceutical Research and Development, Global Biologics, Pfizer Inc., St. Louis, MO 63017, USA. ning.x.li@pfizer.com
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Farrell
authors.initials: F
authors.lastname: Fort
authors.forename: Kendall
authors.initials: K
authors.lastname: Kessler
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D001224:Aspartic Acid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D009842:Oligopeptides; D001224:Aspartic Acid