1 research outputs found
Discovery of Inhibitors of MicroRNA-21 Processing Using Small Molecule Microarrays
The identification
of small molecules that bind to and perturb
the function of microRNAs is an attractive approach for the treatment
for microRNA-associated pathologies. However, there are only a few
small molecules known to interact directly with microRNAs. Here, we
report the use of a small molecule microarray (SMM) screening approach
to identify low molecular weight compounds that directly bind to a
pre-miR-21 hairpin. Compounds identified using this approach exhibit
good affinity for the RNA (ranging from 0.8–2.0 μM) and
are not composed of a polycationic scaffold. Several of the highest
affinity compounds inhibit Dicer-mediated processing, while in-line
probing experiments indicate that the compounds bind to the apical
loop of the hairpin, proximal to the Dicer site. This work provides
evidence that small molecules can be developed to bind directly to
and inhibit miR-21