Strategies for the design of RNA-binding small molecules

Bacterial ribosomal RNA is the target of clinically important antibiotics, while biologically important RNAs in viral and eukaryotic genomes present a range of potential drug targets. The physicochemical properties of RNA present difficulties for medicinal chemistry, particularly when oral availability is needed. Peptidic ligands and analysis of their RNA-binding properties are providing insight into RNA recognition. RNA-binding ligands include far more chemical classes than just aminoglycosides. Chemical functionalities from known RNA-binding small molecules are being exploited in fragment- and ligand-based projects. While targeting of RNA for drug design is very challenging, continuing advances in our understanding of the principles of RNA ligand interaction will be necessary to realize the full potential of this class of targets.