Interaction between a fluoroquinolone derivative KG022 and RNAs: effect of the bulged residues

To progress the RNA-binding small molecule drug discovery, the specific interaction between RNAs having a single bulge and a fluoroquinolone derivative, KG022, was analysed by NMR spectroscopy. In our previous work, it was found that KG022 is located between the two base pairs at the 3' and 5' side of the bulged residue. KG022 prefers G or C as the bulged residue and, in the present study, the reason for this preference was analysed by using RNAs with modified nucleoside residues as the bulged residue. It was found that the amino groups of bulged guanine and cytidine bases interact with the oxygen atoms of the backbone phosphate groups, and the oxygen and nitrogen atoms of bulged guanine and cytidine bases interact with the piperazine group of KG022. Thus, this work presents an example of the mechanism of the specific recognition of a small molecule by RNAs.