Non-coding genes make up approximately 97% of the human genome and have been recognized as playing crucial roles in both disease and health. Among the non-coding genome, RNA holds particular interest due to its diverse regulatory functions in various diseases. Consequently, there has been a significant focus on targeting this portion of the genome through different approaches.
Effective targeting of these RNAs necessitates deep understanding of their biochemistry, as well as insights into their structure and dynamics. Hence, it is crucial to develop optimal methods for characterizing the interaction between compounds and target RNA. NMR spectroscopy, a powerful and unique technique, proves well-suited for investigating different aspects of RNA and small molecules in the early stages of drug discovery.
In my presentation, I will provide an overview of the versatile roles of NMR spectroscopy in RNA drug discovery. This includes its ability to unravel the structural basis for rational drug design, as well as its utility in characterizing the engagement between RNA and potential drug compounds. I will discuss specific labelling schemes that simplify crowded spectra of large RNAs and present a step-by-step approach to verify the interaction between RNA and compounds using NMR spectroscopy. Lastly, I will offer insights into addressing challenges and provide recommendations for performing experiments to characterize RNA structure effectively, without the need for complex structure calculations in the drug discovery process.