title: Kinetics and mechanism of degradation of klerval, a pseudo-tetrapeptide.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Rhone-Poulenc Rorer Research and Development, SW5, Collegeville, USA. chong.won@rp-rorer.com
authors.forename: C M
authors.initials: CM
authors.lastname: Won
authors.forename: T E
authors.initials: TE
authors.lastname: Molnar
authors.forename: V L
authors.initials: VL
authors.lastname: Windisch
authors.forename: R E
authors.initials: RE
authors.lastname: McKean
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009842:Oligopeptides / Q000032:analysis / Q000737:chemistry*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D009842:Oligopeptides; C402262:klerval