科研之友
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摘要
The aim of the present study was the determination of the stability of a diketopiperazine (DKP) derived from the aspartyl tripeptide PheAspGlyOH at pH 10 and 80 degrees C and 25 degrees C as well as at pH 7.4 and 80 degrees C. The analysis was performed using a validated capillary electrophoresis assay. Rapid epimerization of the incubated cis-DKP to the trans-DKP was observed under all conditions. Linear diastereomeric a-l/d-Asp and beta-l/d-Asp peptides were the primary reaction products at pH 10 and 80 degrees C, indicating that a cyclic succinimide is formed in the process. In contrast, the DKPs were by far the major compounds in the incubation solutions at pH 10 and 25 degrees C and at pH 7.4 and 80 degrees C, whereas the linear Asp peptides were found only at low concentrations. A kinetic model was derived to fit the concentration versus time data, which consider the succinimide as central intermediate for DKP formation and for isomerization and enantiomerization of the linear Asp peptides. Besides the back reaction of the DKPs to the succinimides, an additional hydrolysis reaction of the DKP ring was considered to obtain the fit of the experimental data, indicating that additional degradation reactions have to be considered for Asp-derived DKPs.
- 出版日期2012-11
