Degradation of azaglycinamido residues in model tripeptides derived from goserelin.
Three model tripeptides, N-acetyl-Tyr-Pro-azaGly-NH(2) (NYPaG), Tyr-Pro-azaGly-NH(2) (YPaG), and Tyr-Pro-Gly-NH(2)(YPG), were subjected to a systematic degradation study to get information about the degradation of the azaglycinamido residue. The degradation products were characterized with LC-MS. Main degradation products of NYPaG possess partially or totally eliminated azaglycinamido residues, while YPaG and YPG are exhibit cyclo(Tyr-Pro) formation, a diketopiperazine. The influence of the pH on the degradation rate constant k(obs) was investigated for NYPaG and YPaG in the pH range 0.4-11. An U-shaped profile with an inflexion around pH 9 was found for NYPaG while the degradation rate of YPaG was independent of the pH. NYPaG apparently was subject to proton-, solvent-, and hydroxyl-catalyzed degradation reactions whereas YPaG only underwent solvent-catalyzed reactions. Some influence of acetate and phosphate ions on k(obs) was found for YPaG. Arrhenius plots of NYPaG and YPaG were found to be linear.
Hoitink
M A
MA
Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, NL-3584 CA Utrecht, The Netherlands. M.A.Hoitink@pharm.uu.nl
Beijnen
J H
JH
Bult
A
A
Damen
J M
JM
van der Houwen
O A
OA
Kruijtzer
J A
JA
Tibben
M M
MM
Wiese
G
G
Underberg
W J
WJ
D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry; D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017273:Goserelin / Q000737:chemistry*; D006834:Hydrazines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011489:Protein Denaturation; D013816:Thermodynamics
D018931:Antineoplastic Agents, Hormonal; D002021:Buffers; D006834:Hydrazines; D009842:Oligopeptides; D010446:Peptide Fragments; D017273:Goserelin; C010877:carbazic acid