生物活性小分子的靶标鉴定  

Target identification of bioactive small molecules

作　　者：王冬尧[1] 陈啸飞[1] 曹岩[1] 朱臻宇[1] 张俊平[1] 柴逸峰[1] 

机构地区：[1]中国人民解放军第二军医大学药学院,上海200433

出　　处：《中国新药杂志》2015年第10期1119-1123,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81273474;81202496);上海市中药现代化基金(12401900802)

摘　　要：生物活性小分子靶标的明确鉴定需要整合多种分析方法,从多层次、多角度阐明其作用靶标的有效性和专属性。即使这样也都无法排除假阳性或者假阴性的产生,只有各种方法联用才能有力阐明小分子的生物活性与相应靶标。本文系统综述了生物活性小分子靶标鉴定与验证的方法,总结为直接法(包括生物素亲和标签、亲和胶、噬菌体展示、光交联法、亲和磁珠法等)和间接法(包括药物亲和反应靶标分析、蛋白质组学分析、化学基因组学分析和代谢组学分析等)两种。每种方法分别列举了1个实例,并讨论了其优势和劣势,以明确其适用范围和应用前景。The identification and validation of targets for bioactive small molecules need to integrate a vari- ety of analytical methods. The effectiveness and specificity can be confirmed from multi-level and multi-angle. Even so it cannot rule out false positive or false negative results, and only by using a combination of these methods can make it as effectively as possible to illustrate the biological activity and corresponding targets of bioactive small mol- ecules. Target identification and validation methods of these molecules were systematically summarized in this pa- per, including direct methods （biotin-affinity tag, affi-gel tag, phage display, photo-crosslink and high perform- ance affinity magnetic beads） and indirect methods （ drug affinity responsive target stability, proteomic profiling and chemical-genetic profiling）. One example was given to illustrate each method, and the advantages and disadvanta- ges were discussed to clarify its application and prospect.

关 键 词：生物活性小分子 靶标鉴定 直接法 间接法 整合 

分 类 号：R915[医药卫生—微生物与生化药学]