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A Ligand That Targets CUG Trinucleotide Repeats
Author(s) -
Li Jinxing,
Matsumoto Jun,
Bai LiPing,
Murata Asako,
Dohno Chikara,
Nakatani Kazuhiko
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201602741
Subject(s) - myotonic dystrophy , trinucleotide repeat expansion , rna splicing , electrospray ionization , rna , biology , microbiology and biotechnology , gene , chemistry , genetics , computational biology , mass spectrometry , allele , chromatography
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 ( T m ) analyses, surface plasmon resonance (SPR) assay, and electrospray spray ionization time‐of‐flight (ESI‐TOF) mass spectrometry showed that DAP bound to r(CUG) 9 but not to r(CAG) 9 and r(CGG) 9 . The dual luciferase assay clearly indicated DAP bound to the r(CUG) n repeat by affecting the translation in vitro.