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Expansion of cat-ELCCA for the Discovery of Small Molecule Inhibitors of the Pre-let-7–Lin28 RNA–Protein Interaction

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journal contribution
posted on 16.05.2018, 00:00 by Daniel A. Lorenz, Tanpreet Kaur, Samuel A. Kerk, Erin E. Gallagher, Jorge Sandoval, Amanda L. Garner
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.

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