NMR analysis of interaction between RNA structure elements and small molecules.

Abstract

RNA-targeted small molecule drug discovery is widely recognized as an important modality. However, not enough knowledge on the interaction between RNAs and small molecules is accumulated yet. In the present study, 46 RNAs were designed with various internal loops or hairpin loops based on a 29-mer model RNA. The interaction of designed RNAs and three kind of small molecules, risdiplam, naphthyridine carbamate dimer (NCD) and ciprofloxacin, were examined by NMR spectroscopy. The results of interaction experiments were quantitatively analyzed and RNAs interacting with the small molecules were selected. Among the three compounds, NCD shows relatively stronger affinity to some of the model RNAs as judged by the NMR spectra, and binding sites of NCD for two RNAs were determined. The measurement condition used in this work, including the annealing free sample preparation as well as the Mg2+ free sodium phosphate buffer, can be the standard for initial the NMR screening in the RNA-targeted small molecule drug discovery.