金属有机骨架固定化酶及其在中药酶抑制剂筛选中的研究进展

Metal-organic Framework Immobilized Enzyme and Its Application in Screening of Enzyme Inhibitors of Traditional Chinese Medicine:A Review

酶因其高效率、专一性等特点在化工、制药等方面应用广泛,但是游离酶稳定性差、难以回收等不足限制了其应用,因此,酶的固定化及应用成为研究的热点之一。固定化载体的选择为酶固定化的关键步骤,金属有机骨架(MOFs)是由金属离子或金属簇与有机配体配位形成的多孔材料,作为一种新兴的固定化载体,其具有的高孔隙率、强稳定性和表面可修饰性等优点,使其成为理想的固定化酶载体。通过将游离酶固定在MOFs上,可有效解决游离酶上述的不足,大大拓宽了酶的适用环境。配体垂钓是一种从复杂的组分中找寻受体的特异性配体的方法,具有效率高、样品预处理简单和特异性强等优点。酶固定化后形成的MOF-酶复合物可以充当配体垂钓的“钓竿”,将目标物从复杂的组分体系中筛分出来。而中药的化学成分复杂、活性成分多样等特点使得配体垂钓技术在中药酶抑制剂筛选方面大展拳脚,筛选出来的酶抑制剂有望进一步开发成为药效好而不良反应低的先导化合物,因此MOFs固定化酶在中药活性成分筛选中具有广泛的应用前景。基于此,笔者总结了近年来MOFs固定化酶的方法,分析了各方法的特性及优缺点,对制备条件与制备机制的规律进行了总结。同时,对MOFs固定化酶在中药酶抑制剂筛选领域的应用与未来发展进行了总结与展望,以期为后续中药天然成分的开发和中药现代化的发展提供参考。

Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity.However,the shortcomings of the free enzymes,such as poor stability and difficulty in recycling,limit their application.Therefore,the immobilization and application of enzymes have become one of the research hotspots.The selection of the immobilization carriers is a critical step in the process of enzyme immobilization.Metal-organic frameworks(MOFs),a kind of porous materials,are formed by the coordination of metal ions or metal clusters with organic ligands.As an emerging immobilization carrier,its advantages such as high porosity,strong stability,and surface modifiability make it ideal for immobilized enzyme carriers.By immobilizing the free enzyme on MOFs,the above mentioned deficiencies of the free enzymes can be effectively solved,which greatly broaden the applicable condition.Ligand fishing is a method to find receptor-specific ligands from complex components,which has the advantages of high efficiency,simple sample pretreatment and high specificity.The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing,which can screen out the targets from the complex system of components.The complex chemical composition and various active ingredients of traditional Chinese medicine(TCM) make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM.And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects,so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM.Based on this,this paper summarized the methods of immobilized enzymes of MOFs in recent years,analyzed the characteristics,advantages and disadvantages of each method,and summarized the laws of preparation conditions and mechanisms.Meanwhile,the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected,with a view to providing a reference for the development of natural ingredients and the modernization of TCM.