9IOR

INTERACTION BETWEEN A FLUOROQUINOLONE DERIVATIVE KG022 AND RNAS: EFFECT OF BASE PAIRS 5' ADJACENT TO THE BULGE OUT ESIDUES

Summary for 9IOR

• Entry DOI: 10.2210/pdb9ior/pdb
• Descriptor: RNA (5'-R(*GP*GP*AP*UP*AP*CP*UP*UP*UP*CP*GP*AP*GP*UP*GP*AP*UP*CP*C)-3'), 1-cyclopropyl-N-[3-(dimethylamino)propyl]-7-(4-ethylpiperazin-1-yl)-6-fluoranyl-4-oxidanylidene-quinoline-3-carboxamide (2 entities in total)
• Functional Keywords: fluoroquinolone, rna, interaction, specificity
• Biological source: Mus musculus
• Total number of polymer chains: 1
• Total formula weight: 6499.17

Authors

Ichijo, R.,Kawai, G. (deposition date: 2024-07-09, release date: 2025-04-02)

Primary citation

Ichijo, R.,Kawai, G.
Specific Interaction between a Fluoroquinolone Derivative, KG022, and RNAs with a Single Bulge.
Biochemistry, 2025

PubMed Abstract: Small compounds targeting RNAs are recognized as a promising modality in drug discovery. We have found that a fluoroquinolone derivative, KG022, binds to RNAs with single-bulged residues. It has been demonstrated by H NMR that KG022 binds to RNAs with a bulged G or C and a GC or AU base pair at the 3' adjacent to the bulged residues. In the present study, the effects of the base pairs at the 5' adjacent to the bulged residues on the interaction of KG022 were analyzed mainly by H NMR. It was found that KG022 prefers UA and CG base pairs at the 5' adjacent to the bulged residues, indicating that a stable complex is formed by the stacking interaction among the fluoroquinolone ring and the purine bases of the 5' and 3' sides. In addition, this was confirmed by analysis of the F-NMR spectra. Analysis of temperature dependences of NMR spectra revealed that KG022 forms a more stable complex with RNAs having CG base pairs at the 5' adjacent position than those with UA base pairs. This work presented useful information for the development of small molecules having higher affinity to target RNAs.

PubMed: 40067027
DOI: 10.1021/acs.biochem.4c00669

Experimental method

SOLUTION NMR