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

Daniel A Lorenz; Tanpreet Kaur; Samuel A Kerk; Erin E Gallagher; Jorge Sandoval; Amanda L Garner

doi:10.1021/acsmedchemlett.8b00126

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

ACS Med Chem Lett. 2018 May 16;9(6):517-521. doi: 10.1021/acsmedchemlett.8b00126. eCollection 2018 Jun 14.

Authors

Daniel A Lorenz¹, Tanpreet Kaur¹, Samuel A Kerk¹, Erin E Gallagher¹, Jorge Sandoval¹, Amanda L Garner¹

Affiliation

¹ Program in Chemical Biology and Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.

Abstract

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.