Friedrich Schiller University Jena, Department of Pharmaceutical/Medicinal Chemistry, Philosophenweg 14, 07743 Jena, Germany.
Friedrich Schiller University Jena, Department of Pharmaceutical/Medicinal Chemistry, Philosophenweg 14, 07743 Jena, Germany.
J Chromatogr A. 2020 Nov 22;1632:461585. doi: 10.1016/j.chroma.2020.461585. Epub 2020 Sep 25.
The separation of the ll- and dd-enantiomers of the dipeptides Ala-Phe, Ala-phenylglycine (Phg), Ala-homoPhe, Ala-β-Phe, Gly-Phe and β-Ala-Phe was studied by capillary electrophoresis in the presence of negatively charged α-, β- and γ-cyclodextrin (CD) derivatives. Analysis was performed under standardized conditions in fused-silica capillaries at pH 2.5, 3.5 and 5.3. All analyte enantiomers could be separated at pH 2.5 under at least one of the experimental conditions. Especially β-CD derivatives proved to be effective chiral selectors. The enantiomer migration order depended on CD cavity size and substituent type, while peptide structure had only a minor effect. Upon increasing the pH from 2.5 to 5.3, reversal of the enantiomer migration order was observed frequently. Investigation of the apparent and, in the case of randomly substituted CDs, averaged complexation constants and mobilities of the diastereomeric peptide enantiomer-CD complexes indicated that in most cases the migration order in the presence of sulfated α-, β- and γ-CD and heptakis(6-O-sulfo)-β-CD could be explained by the stronger binding of the second migrating analyte by the CD at pH 2.5. However, in few cases the weaker bound enantiomer migrated second, which could be attributed to the higher mobility of the respective CD complexes. At pH 5.3, similar data were obtained for sulfated β-CD and heptakis(6-O-sulfo)-β-CD, i.e. the strength of the complexes determined the migration order for some peptides, while the migration sequence was based on the apparent (and averaged) mobility of the diastereomeric analyte-CD complexes in other cases.
在存在带负电荷的 α-、β-和 γ-环糊精（CD）衍生物的情况下，通过毛细管电泳研究了二肽 Ala-Phe、Ala-苯甘氨酸（Phg）、Ala-homoPhe、Ala-β-Phe、Gly-Phe 和 β-Ala-Phe 的 ll-和 dd-对映异构体的分离。在 pH 2.5、3.5 和 5.3 下，在标准条件下在熔融石英毛细管中进行分析。在至少一种实验条件下，所有分析物对映异构体都可以在 pH 2.5 下分离。特别是 β-CD 衍生物被证明是有效的手性选择剂。对映体迁移顺序取决于 CD 腔大小和取代基类型，而肽结构只有较小的影响。当 pH 从 2.5 增加到 5.3 时，经常观察到对映体迁移顺序的反转。对非对映体肽对映体-CD 配合物的表观和（在随机取代的 CD 的情况下）平均络合常数和迁移率的研究表明，在大多数情况下，在存在硫酸化的 α-、β-和 γ-CD 和 heptakis(6-O-sulfo)-β-CD 的情况下，迁移顺序可以通过 CD 在 pH 2.5 下更强地结合第二个迁移分析物来解释。然而，在少数情况下，较弱结合的对映体迁移第二，这可以归因于各自的 CD 配合物的更高迁移率。在 pH 5.3 下，对于硫酸化的 β-CD 和 heptakis(6-O-sulfo)-β-CD 也获得了类似的数据，即对于一些肽，配合物的强度决定了迁移顺序，而在其他情况下，迁移序列基于非对映体分析物-CD 配合物的表观（和平均）迁移率。
