蛋白质类手性固定相的研究进展及其在药物手性拆分中的应用

Research Progress of Protein-based Chiral Stationary Phases and Their Applications to Chiral Drug Resolution

手性药物的色谱拆分方法包括手性衍生化试剂法、手性流动相添加剂法和手性固定相法等。随着大量商品化手性固定相色谱柱的出现,手性固定相法以其快速、简便、高效的特点,迅速在药物手性拆分领域占据主导地位。蛋白质类手性固定相是应用最为广泛的手性固定相之一,它能够提供多种类型的相互作用力和手性识别位点,对不同类型的药物具有广泛的手性识别能力。本文综述了蛋白质类手性固定相的研究进展,及近3年其在药物手性拆分中的应用,讨论了各种固定相的性质特点、适用范围、影响药物手性拆分的因素以及色谱方法优化流程等。

Chromatographic resolution of chiral drugs includes three kinds of approaches, namely chiral derivatization approach, chiral mobile phase approach, and chiral stationary phase （CSP） approach. Along with the emerge of a large number of commercially available CSP columns, the CSP approach quickly dominates the field of chiral drug resolution, due to its various advantages of high speed, simplicity, and efficiency. Protein-based CSPs remain one of the most widely used CSPs, and exhibit enantioselectivity for a wide range of compounds because of multiple binding sites on the surface of chiral selectors and multiple binding interactions between chiral selectors and ligands. This review mainly focuses on the research progress of protein-based CSPs and their applications to chiral drug resolution in recent 3 years, with the emphasis on their enantioselective properties, application scope, the factors influencing drug resolution, and a chromatographic optimization scheme on these stationary phases.