TY - JOUR
T1 - A Ligand That Targets CUG Trinucleotide Repeats
AU - Li, Jinxing
AU - Matsumoto, Jun
AU - Bai, Li Ping
AU - Murata, Asako
AU - Dohno, Chikara
AU - Nakatani, Kazuhiko
N1 - Funding Information:
This work was supported by the JSPS KAKENHI Grant-in-Aid for Specially Promoted Research (JP26000007) for K.N. Authors also thank Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science, and Technology, Japan for the technical support on using molecular-modeling software (SCHRÖDINGER Suit).
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/10/10
Y1 - 2016/10/10
N2 - 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.
AB - 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.
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U2 - 10.1002/chem.201602741
DO - 10.1002/chem.201602741
M3 - Article
C2 - 27573860
AN - SCOPUS:84989897731
SN - 0947-6539
VL - 22
SP - 14881
EP - 14889
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 42
ER -