Interaction between a fluoroquinolone derivative and RNAs with a single bulge

Abstract

Interaction analysis between small molecules and RNA as well as structure determination of RNA-small molecule complexes will be the clues to search for compounds that bind to specific mRNA or non-coding RNA in drug discovery. In this study, the RNA-binding ability of a fluoroquinolone derivative, KG022, was examined against single-residue bulge-containing hairpin RNAs as RNA models. Nuclear magnetic resonance analysis indicated that KG022 interacts with the RNAs in the vicinity of the bulge residue, with preferring C and G as the bulge residues. The solution structures of the RNA-KG022 complexes showed that the KG022 binds to the RNAs at the bulge-out regions. Each substituent in KG022 interacts with specific position of RNAs around the bulge-out region probably contributing the specificity of the binding. This work provides a novel member for the RNA-targeted small molecules.

Keywords: NMR; RNA; fluoroquinolone; interaction; small molecule.