Publication – Schwalbe, Wöhnert

RNA as drug target, in NMR of Biomolecules: Towards Mechanistic Systems Biology.

Ferner JP, Duchardt-Ferner E, Rinnenthal J, Buck J, Wöhnert J, Schwalbe H. NMR of Biomolecules: Towards Mechanistic Systems Biology, 2012 Mar. Abstract or full publication here.

The discovery of many novel biological functions for RNA and the realization that many functional RNAs adopt highly intricate three-dimensional structures have led to a growing interest in exploiting RNA as a drug target. NMR spectroscopy in solution has emerged as a highly versatile technique for characterizing the interaction of RNAs with small molecules for a wide range of affinities at different levels of detail ranging from simple detection of binding events in library screening experiments to a full high-resolution structural characterization of RNA–small-molecule complex structures. The NMR spectroscopic techniques that are employed to investigate RNA–small-molecule interactions are very similar to those developed for proteins. However, RNA has a number of biophysical and NMR spectroscopic characteristics that are distinctly different from those of proteins. Accordingly, on one hand, experiments developed for proteins need to be carefully adapted to the special properties of RNA molecules. On the other hand, RNAs offer unique possibilities that sometimes even simplify the experiments for investigating RNA–ligand interactions. This chapter describes the features that render RNAs especially suitable for studying macromolecule–ligand interactions as well as giving a rationale for the required adaptations in experiments originally developed for protein applications, and describes the most popular approaches in detail using examples from our own work in the field of RNA–ligand interactions.