Inhibition of DNA replication by a d(CAG) repeat binding ligand.
Trinucleotide repeat expansions in genomic DNA are the molecular basis of a number of genetic diseases. The (CAG)n, (CTG)n, and (CGG)n repeats share the common sequence CXG, and inherently produce a hairpin structure involving X-X mismatch base pairs flanked by two G-C base pairs. The chance of a strand slippage leading to the repeat expansion is considered to increase with increasing stability of the hairpin form. Here we show our synthetic ligand naphthyridine-azaquinolone (NA) stabilized a hairpin form of the (CAG)n repeat and inhibited the polymerase-mediated DNA synthesis.
Hagihara
Masaki
M
The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047, Japan.
Nakatani
Kazuhiko
K
D000225:Adenine / Q000737:chemistry; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006147:Guanine / Q000737:chemistry; D006860:Hydrogen Bonding; D008024:Ligands; D009287:Naphthyridines / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D015363:Quinolones / Q000737:chemistry*; D019680:Trinucleotide Repeat Expansion
C522086:7-(4-aza-6-(7-methylnaphthyridin-2-ylcarbonyl)hexanamidomethyl)-8-azaquinolone; D008024:Ligands; D009287:Naphthyridines; D015363:Quinolones; D006147:Guanine; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D000225:Adenine