Fluorescence Probe for Detecting CCG Trinucleotide Repeat DNA Expansion and Slip-Out

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. Fluorescence detection of trinucleotide repeats: The tricyclic ligand, Am‐BzN, can be used as a fluorescence probe for the detection of CCG trinucleotide repeat expansion and slip‐out structures. The fluorescence probe will be a useful tool for biophysical and biochemical studies on CCG trinucleotide repeat DNA.