A small molecule regulates hairpin structures in d(CGG) trinucleotide repeats.
Unusual expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases. Although the actual mechanism of repeat expansion remains uncertain, trinucleotide repeat instability may be related to the increased stability of an alternative DNA hairpin structure formed in the repeat sequences. Here we report that a synthetic ligand naphthyridine carbamate dimer (NCD) selectively bound to and stabilized an intra-stranded hairpin structure in CGG repeat sequences. The NCD-CGG hairpin complex was a stable structure that efficiently interfered with DNA replication by Taq DNA polymerase. Considering the sequence preference of NCD, the use of NCD would be valuable to investigate the genetic instabilities of CGG/CCG repeat sequences in human genomes.
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
Masaki
M
Hagihara
Hanping
H
He
Maki
M
Kimura
Kazuhiko
K
Nakatani
D001483:Base Sequence; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D004261:DNA Replication / Q000187:drug effects; D019281:Dimerization; D006801:Humans; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology*; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D018911:Trinucleotide Repeats / Q000187:drug effects*
D002219:Carbamates; D009287:Naphthyridines; D054852:Small Molecule Libraries; D004247:DNA