Fragment-Based Approaches to Identify RNA Binders

Although fragment-based drug discovery (FBDD) has beensuccessfullyimplemented and well-explored for protein targets, its feasibilityfor RNA targets is emerging. Despite the challenges associated withthe selective targeting of RNA, efforts to integrate known methodsof RNA binder discovery with fragment-based approaches have been fruitful,as a few bioactive ligands have been identified. Here, we review variousfragment-based approaches implemented for RNA targets and provideinsights into experimental design and outcomes to guide future workin the area. Indeed, investigations surrounding the molecular recognitionof RNA by fragments address rather important questions such as thelimits of molecular weight that confer selective binding and the physicochemicalproperties favorable for RNA binding and bioactivity.