title: BzDANP, a Small-Molecule Modulator of Pre-miR-29a Maturation by Dicer.
abstract: 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.
authors.affiliation: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University , 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Murata
authors.affiliation: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University , 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Otabe
authors.affiliation: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University , 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University , 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakatani
mesh_terms: D035683:MicroRNAs / Q000378:metabolism*; D009287:Naphthyridines / Q000494:pharmacology*; D012322:RNA Precursors / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013696:Temperature
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D009287:Naphthyridines; D012322:RNA Precursors; D043244:Ribonuclease III