Kinetics and mechanism of degradation of klerval, a pseudo-tetrapeptide.
The degradation of klerval (I) was studied as a function of pH. The extent and routes of degradation were found to be pH-dependent. Under strongly acidic conditions (pH<2), the drug predominantly undergoes specific acid-catalyzed hydrolysis of the side-chain amide bond yielding II8), the drug undergoes specific base-catalyzed hyrolysis yielding II and epimerization generating D-epimer. The epimerization appears to occur via the succinimide intermediate in neutral pH region. With increasing pH, however, the epimerization rate increases due to direct epimerization of the peptides.
Won
C M
CM
Department of Pharmaceutical Sciences, Rhone-Poulenc Rorer Research and Development, SW5, Collegeville, USA. chong.won@rp-rorer.com
Molnar
T E
TE
Windisch
V L
VL
McKean
R E
RE
D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009842:Oligopeptides / Q000032:analysis / Q000737:chemistry*; D013237:Stereoisomerism; D013997:Time Factors
D009842:Oligopeptides; C402262:klerval