生物活性小分子的靶标鉴定

Target identification of bioactive small molecules

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.