Key result
Naphthyridine carbamate dimer (NCD) showed relatively stronger affinity to some of the 46 model RNAs as judged by NMR spectra, and binding sites of NCD for two RNAs were determined.
Why the study?
RNA-targeted small molecule drug discovery is an important modality, but knowledge on the interaction between RNAs and small molecules remains limited.
The study establishes a standard measurement condition for initial NMR screening in RNA-targeted small molecule drug discovery.
Sets NMR screening benchmark for RNA ligands; extends early discovery but leaves clinical translation open.
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 kinds of small molecules, risdiplam, naphthyridine carbamate dimer (NCD) and ciprofloxacin, were examined by nuclear magnetic resonance (NMR) spectroscopy. The results of interaction experiments were quantitatively analysed 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 the initial NMR screening in the RNA-targeted small molecule drug discovery.
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Tomemori et al. (2025) studied this question. risdiplam, naphthyridine carbamate dimer (NCD) and ciprofloxacin was evaluated on Interaction between RNAs and small molecules. Naphthyridine carbamate dimer (NCD) showed relatively stronger affinity to some of the 46 model RNAs as judged by NMR spectra, and binding sites of NCD for two RNAs were determined.
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