Identification and investigation of RNA-binding ligands

Myotonic dystrophy type 1 is caused by a toxic CUG RNA repeat expansion in the 3’-UTR of the DMPK gene that sequesters a key splicing regulator, MBNL1, preventing normal modulation of alternative splicing of a variety of genes. Targeting these repeats with small molecules could block the sequestration of MBNL1 and restore normal splicing levels, alleviating the pathogenesis of the disease. To that end, I have screened a library of select compounds, chosen for their potential to act as RNA binding ligands. From the initial screen, I identified several promising lead compounds. I proceeded to perform a structure-activity relationship (SAR) study on one of the lead molecules, NSC657704. Based on the results of the SAR, I designed a set of derivatives, synthesized them, and ascertained their inhibitory activity and RNA binding affinity