In the past year, two lines of research yielded publications. The TPP riboswitch is widely distributed phylogenetically. Previously, our collaborator Dr. Abell and coworkers have carried out a fragment-based screen against this riboswitch and found a number of small organic molecules that bind with high specificity, albeit low affinity, to the RNA. Fragment-based screening is predicated on being able to elucidate the binding location of the low affinity fragments so that they can be elaborated into high affinity binders. Crystallographic work in our laboratory has confirmed the specificity of binding of a number of fragments, and elaboration of these into more potent ligands for the TPP riboswitch is underway. In collaboration with Dr. Wang we have also developed novel methodology for the synthesis of RNAs with position-selective labeling. Such RNAs are vial tools for high-throughput screening in vitro relying on conformational readout through FRET.
