BzDANP, a Small-Molecule Modulator of Pre-miR-29a Maturation by Dicer

We here report the synthesis of novel molecule BzDANP having a three-ring benzo­[c]­[1,8]­naphthyridine system, the evaluation of its binding properties to a single nucleotide bulge in RNA duplexes, and BzDANP-induced suppression of pre-miR-29a processing by Dicer. BzDANP showed much increased affinity to the bulged RNAs as compared with the parent molecule DANP, which possesses the same hydrogen-bonding surface as BzDANP but in a two-ring [1,8]­naphthyridine system. Melting temperature analysis of bulged RNAs showed that BzDANP most effectively stabilized the C-bulged RNA. Dicer-mediated processing of pre-miR-29a was suppressed by BzDANP in a concentration dependent manner. The presence of the C-bulge at the Dicer cleavage site was effective for the suppression of pre-miR-29a processing by BzDANP. These results demonstrated that the small molecule binding to the bulged site in the vicinity of the Dicer cleavage site could be a potential modulator for the maturation of pre-miRNA