title: Fluorescence Probe for Detecting CCG Trinucleotide Repeat DNA Expansion and Slip-Out.
abstract: Trinucleotide repeat expansion in genomic DNA causes severe neurodegenerative diseases. Fluorescence probes that bind to trinucleotide repeats have potential as diagnostic tools of trinucleotide repeat disorders. Here, we report a novel tricyclic ligand that binds to CCG trinucleotide repeat DNA. The expansion of the aromatic ring system of the 2-amino-1,8-naphthyridine chromophore from the bicyclic to the tricyclic improved the binding ability to the CCG/CCG motif without losing the selectivity and emissive character. The fluorescence sensitively decreased in response to binding to the CCG trinucleotide repeat. The degree of quenching depended on the number of CCG repeats. In addition, the fluorescence detection was applicable to CCG slip-out DNA.
authors.affiliation: Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, 567-0047, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, 567-0047, Japan. nakatani@sanken.osaka-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakatani
mesh_terms: D004247:DNA / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D005456:Fluorescent Dyes / Q000032:analysis* / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D004247:DNA
keywords: (CCG)n repeat; fluorescence probes; hydrogen bonds; molecular recognition; slip-out DNA