Strategies for the design of RNA-binding small molecules

Abstract

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.