Abstract:

Adsorptive protein chromatography, mostly based on ion exchange, affinity binding and hydrophobic interactions, is the key technology in the large-scale production of therapeutic proteins. The development of novel technology as well as improvement of chromatographic separation efficiency, such as dynamic binding capacity and selectivity, is generally the main objective of fundamental studies on protein chromatography. Recently, polymeric ligand-modified matrices have been developed and widely studied due to the findings that some of them not only possess high equilibrium adsorption capacity but also high uptake rate. This review is devoted to an overview of the polymeric ligands for protein chromatography. Different kinds of polymeric ligands are first introduced. This is followed by the effects and functional mechanisms of the polymeric ligand chemistry on protein adsorption equilibria, uptake kinetics as well as separation performance of the ligand-modified matrices. Applications of the matrices based on the mechanisms are then illustrated to offer insight into the design of new polymeric ligands. Finally, a perspective for further development and fundamental studies on polymeric ligand-based protein chromatography is discussed.

Key words: protein, adsorption, chromatography, polymer grafting, ligand

摘要：

以离子交换、亲和结合和疏水性吸附为主的蛋白质吸附层析是药用蛋白质生产过程的核心技术,开发新技术和提高蛋白质吸附层析操作的分离效率(如选择性和动态吸附容量等)是该领域的主要研究目标。近年来聚合物配基接枝的层析介质由于同时具有较高的吸附容量和传质速率,得到产学界的广泛关注。本文针对聚合物配基接枝修饰的蛋白质吸附层析介质的配基化学特征、吸附和传质特性、层析分离应用和设计等方面进行评述。首先介绍不同种类的聚合物接枝介质,然后系统阐述聚合物配基化学特性对介质吸附和传质性能的影响机制,并分析上述性质对聚合物配基接枝层析介质分离特性的影响机理和应用,最后讨论和展望了高效聚合物配基接枝介质设计、开发和应用的前景。

关键词: 蛋白质, 吸附, 层析, 聚合物接枝, 配基