Solution structure of a small-molecular ligand complexed with CAG trinucleotide repeat DNA.
NMR structure of the first identified ligand, naphthyridine-azaquinolone (NA), complexed with the CAG-CAG triad is reported. The determined structure revealed the invasive ligands binding to the A-A mismatch and flanking G-C base pairs, causing the widowed cytosines to flip out from pi-stack. Hydrogen-bond pairs between NA and DNA, naphthyridine-guanine and azaquinolone-adenine, are well stacked in the right-handed DNA helix, showing structural mimicry of Watson-Crick base pairing. This is the first observation that the small molecular ligand induced the base flipping of the nucleotide base in the Watson-Crick base pair.
Nakatani
Kazuhiko
K
Graduate School of Engineering, Kyoto University, Kyoto 618-8510, Japan.
Hagihara
Shinya
S
Goto
Yuki
Y
Kobori
Akio
A
Hagihara
Masaki
M
Hayashi
Gosuke
G
Kyo
Motoki
M
Nomura
Makoto
M
Mishima
Masaki
M
Kojima
Chojiro
C
D020029:Base Pairing; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D009287:Naphthyridines / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D015363:Quinolones / Q000737:chemistry*; D012996:Solutions; D018911:Trinucleotide Repeats
C520187:(7-methylnaphthyridin-2-ylcarbmoylethyl)(8-azaquinolonecarbamoyl)amine; D008024:Ligands; D009287:Naphthyridines; D015363:Quinolones; D012996:Solutions