ml8b00126_si_001.pdf (4.08 MB)
Download fileExpansion of cat-ELCCA for the Discovery of Small Molecule Inhibitors of the Pre-let-7–Lin28 RNA–Protein Interaction
journal contribution
posted on 2018-05-16, 00:00 authored by Daniel
A. Lorenz, Tanpreet Kaur, Samuel A. Kerk, Erin E. Gallagher, Jorge Sandoval, Amanda L. GarnerDysregulation 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.