Interaction between a fluoroquinolone derivative KG022 and RNAs: Effect of base pairs 3′ adjacent to the bulged residues

RNA-targeted small molecules are a promising modality in drug discovery. Recently, we found that a fluoroquinolone derivative, KG022, can bind to RNAs with bulged C or G. To clarify the RNA specificity of KG022, we analyzed the effect of the base pair located at the 3′side of the bulged residue. It was found that KG022 prefers G-C and A-U base pairs at the 3′side. Solution structures of the complexes of KG022 with the four RNA molecules with bulged C or G and G-C or A-U base pairs at the 3′side of the bulged residue were determined to find that the fluoroquinolone moiety is located between two purine bases, and this may be the mechanism of the specificity. This work provides an important example of the specificity of RNA-targeted small molecules.