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

被引:19
作者
Murata, Asako [1 ]
Otabe, Takahiro [1 ]
Zhang, Jinhua [1 ]
Nakatani, Kazuhiko [1 ]
机构
[1] Osaka Univ, Inst Sci & Ind Res, Dept Regulatory Bioorgan Chem, 8-1 Mihogaoka, Osaka 5670047, Japan
关键词
GUANINE-GUANINE MISMATCHES; SURFACE-PLASMON RESONANCE; HELIX-THREADING PEPTIDES; TARGETING RNA; NONCODING RNAS; IN-VIVO; ONCOGENIC MICRORNAS; NUCLEIC-ACIDS; HIGH-AFFINITY; DIMERIC FORM;
D O I
10.1021/acschembio.6b00214
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2790 / 2796
页数:7
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