Exploiting small molecule binding to DNA for the detection of single-nucleotide mismatches and their base environment.
Naphthyridine-azaquinolone (Npt-Azq, described previously by Nakatani et al. ( Nakatani, K.; Hagihara, S.; Goto, Y.; Kobori, A.; Hagihara, M.; Hayashi, G.; Kyo, M.; Nomura, M.; Mishima, M.; Kojima, C. Nat. Chem. Biol. 2005, 1, 39-43.), was exploited to detect an adenine-adenine mismatch with a symmetrical G-C flanking sequence (5'-GAC-3'/5'-CAG-3') in a synthetic 20-mer DNA by electrochemical impedance spectroscopy. This innovative strategy enables us to obtain information about the presence of a specific mismatch in addition to sequence information. Npt-Azq binds the G-A region of the mismatch, which causes significant changes in the structure of the DNA, which in turn causes changes in the electrochemical properties of DNA/Npt-Azq films. For a 20-mer DNA containing an A-A mismatch, the electron-transfer resistance (RCT) of the system is significantly different in the presence of bound Npt-Azq, presumably due to the structural differences in the two films. Npt-Azq does not bind to matched DNA, and thus, the presence of Npt-Azq does not affect the electrochemical properties of such films.
Li
Xiaohong
X
Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan, S7N 5C9, Canada.
Song
Haifeng
H
Nakatani
Kazuhiko
K
Kraatz
Heinz-Bernhard
HB
D004247:DNA / Q000032:analysis* / Q000737:chemistry*; D004566:Electrodes; D008024:Ligands; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry; D009711:Nucleotides / Q000032:analysis* / Q000737:chemistry*
D008024:Ligands; D009287:Naphthyridines; D009711:Nucleotides; D004247:DNA