A Ligand That Targets CUG Trinucleotide Repeats

Jinxing Li, Jun Matsumoto, Li Ping Bai, Asako Murata, Chikara Dohno, Kazuhiko Nakatani

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

The development of small molecules that can recognize specific RNA secondary and tertiary structures is currently an important research topic for developing tools to modulate gene expression and therapeutic drugs. Expanded CUG trinucleotide repeats, known as toxic RNA, capture the splicing factor MBNL1 and are causative of neurological disorder myotonic dystrophy type 1 (DM1). Herein, the rational molecular design, synthesis, and binding analysis of 2,9-diaminoalkyl-substituted 1,10-phenanthroline (DAP), which bound to CUG trinucleotide repeats, is described. The results of melting temperature (Tm) analyses, surface plasmon resonance (SPR) assay, and electrospray spray ionization time-of-flight (ESI-TOF) mass spectrometry showed that DAP bound to r(CUG)9but not to r(CAG)9and r(CGG)9. The dual luciferase assay clearly indicated DAP bound to the r(CUG)nrepeat by affecting the translation in vitro.

Original languageEnglish
Pages (from-to)14881-14889
Number of pages9
JournalChemistry - A European Journal
Volume22
Issue number42
DOIs
Publication statusPublished - Oct 10 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

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