Factors affecting cleavage at aspartic residues in model decapeptides.
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.
Li
Ning
N
Pharmaceutical Research and Development, Global Biologics, Pfizer Inc., St. Louis, MO 63017, USA. ning.x.li@pfizer.com
Fort
Farrell
F
Kessler
Kendall
K
Wang
Wei
W
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
D009842:Oligopeptides; D001224:Aspartic Acid