Fragment-based approaches to identify RNA binders

Although fragment-based drug discovery (FBDD) has been successfully implemented and well-explored for protein targets, its feasibility for RNA targets is emerging. Despite the challenges associate with the selective targeting of RNA, efforts to integrate known methods of RNA binder discovery with fragment-based approaches has been fruitful, as a few bioactive ligands have been identified. Here, we review various fragment-based approaches implemented for RNA targets and provide insight into experimental design and outcomes, to guide future work in the area. Indeed, investigations surrounding the molecular recognition of RNA by fragments address rather important questions such as the limits of molecular weight that confers selective binding and the physicochemical properties favorable for RNA binding and bioactivity.