天然产物是创新药物的主要源泉，其活性成分快速靶向分离分析是热点和难点问题。本项目针对天然产物成分复杂多样、难于快速分离分析、易变等特点，结合课题组在分离分析新方法研究中形成的基础和优势，开展基于功能化纳米Fe3O4材料的天然产物中酶抑制剂快速靶向分离分析新方法，即制备稳定、特异性强、磁响应强的酶(三种II型糖尿病药靶：蛋白酪氨酸磷酸酯酶-1B，二肽基肽酶IV和α-葡萄糖苷酶)负载的纳米Fe3O4材料，基于亲和吸附原理，在分子水平上快速靶向分离天然产物中酶抑制剂；配以HPLC-MS/MS分析鉴定；并采用HSCCC导向制备活性成分；建立集靶向分离-高通量分析-高效制备于一体的天然产物中酶抑制剂快速分离分析新方法，以期获得大量结构新颖的活性成分。同时系统研究各单体的构效关系以及化合物之间的协同作用机理。研究成果为天然产物活性成分的快速分离分析提供一个简便、高效、灵敏、特异性强的研究思路和方法。

Natural products have historically been invaluable as a source of therapeutic agents, however, the major bottleneck that continues to affect drug discovery is the target purification and analysis of active compounds from the complex extract, since natural products have many active compounds with different polarities and concentrations and sometimes the structures of the compounds would change because of the decomposition. As part of our continuous efforts on rapid screening and isolation of active compounds from natural products, the present work described a novel-immobilized enzyme strategy on Fe3O4 nanospheres for target purification and analysis of active compounds from natural products due to its high sensitivity and specifity, excellent suspension stability and convenient solid-liquid separation. PTP 1B, DPP IV and α-glucosidase (three drug targets for type 2 diabetes) were stably immobilized onto Fe3O4 magnetic nanospheres, respectively, and then the functional magnetic nanospheres were used to screen and isolate active compounds from the corresponding natural extracts. HPLC-MS/MS was used for compounds analysis and identification, while HSCCC was applied for the preparative purification of target compounds. Moreover, the structure-activity relationships and synergies of all active compounds were interpreted. The present work demonstrated a facile way with high efficiency and specificity to purify and identify active compounds from complex natural products.