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Updated: Jul 18, 2026
10:23
Self-assembly of Complex Two-dimensional Shapes from Single-stranded DNA Tiles
Published on: May 8, 2015
Solution structure of a small-molecular ligand complexed with CAG trinucleotide repeat DNA
Kazuhiko Nakatani1, Shinya Hagihara, Yuki Goto
1Graduate School of Engineering, Kyoto University, Kyoto 618-8510, Japan.
Nucleic Acids Symposium Series (2004)
|December 8, 2006
Summary
The first identified ligand, naphthyridine-azaquinolone (NA), binds to DNA mismatches, causing base flipping. This small molecule ligand mimics Watson-Crick pairing, a novel observation in DNA-ligand interactions.
Area of Science:
- Structural biology
- Medicinal chemistry
- Molecular genetics
Background:
- Small molecule ligands are crucial for modulating DNA structure and function.
- Understanding ligand-DNA interactions at the atomic level is key to drug design.
- DNA base mismatches and their structural consequences are important in genetic stability and disease.
Purpose of the Study:
- To determine the NMR structure of the naphthyridine-azaquinolone (NA) ligand complexed with a CAG-CAG DNA triad.
- To elucidate the binding mode and structural effects of NA on DNA, particularly at mismatch sites.
- To investigate the potential of NA to induce novel DNA structural changes, such as base flipping.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine the three-dimensional structure of the DNA-ligand complex.
- Detailed structural analysis focused on ligand-DNA interactions, base pairing, and helix geometry.
- Comparative analysis with known DNA structures was performed to identify unique binding events.
Main Results:
- The NMR structure revealed the naphthyridine-azaquinolone (NA) ligand binding to an A-A mismatch and adjacent G-C base pairs within the CAG-CAG DNA triad.
- NA binding induced cytosine bases to flip out from the DNA pi-stack, a phenomenon termed base flipping.
- Hydrogen bonding interactions between NA and DNA bases (naphthyridine-guanine, azaquinolone-adenine) were observed, mimicking Watson-Crick base pairing within the right-handed DNA helix.
Conclusions:
- This study reports the first NMR structure of the naphthyridine-azaquinolone (NA) ligand complexed with DNA.
- The findings demonstrate that small molecular ligands can induce base flipping in Watson-Crick base pairs, a previously unobserved mechanism.
- The structural mimicry of Watson-Crick pairing by NA highlights its potential as a novel therapeutic agent targeting specific DNA structures.
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