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

Asako Murata, Takahiro Otabe, Jinhua Zhang, Kazuhiko Nakatani

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2790-2796
Number of pages7
JournalACS Chemical Biology
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 21 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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