Antti Henrik, Sellstedt Magnus
Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
ACS Med Chem Lett. 2018 Mar 8;9(4):351-353. doi: 10.1021/acsmedchemlett.7b00535. eCollection 2018 Apr 12.
Finding a new drug candidate for a selected target is an expensive and time-consuming process. Target guided-synthesis, or click chemistry, is a concept where the drug target is used to template the formation of its own inhibitors from reactive building blocks. This could simplify the identification of drug candidates. However, with the exception of one example of an RNA-target, target-guided synthesis has always employed purified targets. This limits the number of targets that can be screened by the method. By applying methods from the field of metabolomics, we demonstrate that target-guided synthesis with protein targets also can be performed directly in cell-based systems. These methods offer new possibilities to conduct screening for drug candidates of difficult protein targets in cellular environments.
为选定的靶点寻找新的候选药物是一个昂贵且耗时的过程。靶点导向合成，即点击化学，是一种利用药物靶点作为模板，从反应性构建模块中形成其自身抑制剂的概念。这可以简化候选药物的识别过程。然而，除了一个RNA靶点的例子外，靶点导向合成一直使用纯化的靶点。这限制了该方法能够筛选的靶点数量。通过应用代谢组学领域的方法，我们证明了与蛋白质靶点的靶点导向合成也可以直接在基于细胞的系统中进行。这些方法为在细胞环境中筛选难成药的蛋白质靶点的候选药物提供了新的可能性。
