Modularly assembled small molecules for the treatment of myotonic dystrophy type 1

To study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the noncoding expanded RNA repeat that causes myotonic dystrophy type 1 (Dm1), r(CUG)exp. Different modular assembly scaffolds were investigated including polyamines, alpha-peptides, beta-peptides, and peptide tertiary amides (PT As). Based on activity as assessed by improvement of DM1 -associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely PT As, are optimal.