Dysregulation of microRNA (miRNA) expression has been linked to many human diseases; however, because of the challenges associated with RNA-targeted drug discovery, additional approaches are needed for probing miRNA biology. The emerging regulatory role of miRNA-binding proteins in miRNA maturation presents such an alternative strategy. Exploiting our laboratory’s click chemistry-based high-throughput screening (HTS) technology, catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a modular method by which to discover new chemical tools for manipulating pre-miRNA–miRNA–binding protein interactions. Using the pre-let-7d–Lin28 interaction as proof-of-concept, the results presented demonstrate how HTS using cat-ELCCA can enable the discovery of small molecules targeting RNA–protein interactions.

中文翻译：

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扩展cat-ELCCA，以发现Pre-let-7–Lin28 RNA–蛋白质相互作用的小分子抑制剂

microRNA（miRNA）表达失调与许多人类疾病有关。但是，由于与靶向RNA的药物发现相关的挑战，因此需要其他方法来探测miRNA生物学。miRNA结合蛋白在miRNA成熟中的新兴调控作用提出了这种替代策略。利用我们实验室基于点击化学的高通量筛选（HTS）技术，催化酶联点击化学分析或cat-ELCCA，我们设计了一种模块化方法，可通过该方法发现用于操纵前miRNA–miRNA结合的新化学工具。蛋白质相互作用。使用pre-let-7d-Lin28相互作用作为概念验证，所呈现的结果证明了使用cat-ELCCA的HTS如何能够发现靶向RNA-蛋白相互作用的小分子。