title: A Ligand That Targets CUG Trinucleotide Repeats.
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.
authors: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, 567-0047, Japan.
authors: Jinxing
authors: J
authors: Li
authors: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, 567-0047, Japan.
authors: Jun
authors: J
authors: Matsumoto
authors: State Key Laboratory of Quality Research in Chinese Medicine and, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors: Li-Ping
authors: LP
authors: Bai
authors: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, 567-0047, Japan.
authors: Asako
authors: A
authors: Murata
authors: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, 567-0047, Japan.
authors: Chikara
authors: C
authors: Dohno
authors: Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, 567-0047, Japan. nakatani@sanken.osaka-u.ac.jp.
authors: Kazuhiko
authors: K
authors: Nakatani
mesh_terms: D006801:Humans; D008024:Ligands; D009223:Myotonic Dystrophy / Q000378:metabolism*; D010618:Phenanthrolines / Q000737:chemistry*; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000502:physiology*; D018911:Trinucleotide Repeats / Q000187:drug effects*
chemical_list: D008024:Ligands; D010618:Phenanthrolines; D016601:RNA-Binding Proteins; D012313:RNA; C025205:1,10-phenanthroline
keywords: (CUG)n repeats; RNA; SPR; small molecules; translation