A new small molecule DoNA binding to CAG repeat RNA

被引：1
|
作者：
Chen, Qingwen [1 ]
Yamada, Takeshi [1 ,3 ]
Miyagawa, Koichi [2 ]
Murata, Asako [1 ,4 ]
Shoji, Mitsuo [2 ]
Nakatani, Kazuhiko [1 ]
机构：
[1] Osaka Univ, Inst Sci & Ind Res, SANKEN, 8-1 Mihogaoka, Ibaraki 5670047, Japan
[2] Univ Tsukuba, Ctr Computat Sci, Tsukuba, Ibaraki 3058577, Japan
[3] Tokyo Med & Dent Univ, Nucleotide & Peptide Drug Discovery Ctr, 1-5-45 Yushima,Bunkyo ku, Tokyo 1138519, Japan
[4] Kyushu Univ, Fac Engn Sci, Dept Mat Sci, 6-1 Kasuga koen,Kasuga, Fukuoka 8168580, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2024年 / 98卷
关键词：
DoNA; RNA binding small molecule; CAG repeats; HUNTINGTONS-DISEASE; DNA; PATHOGENESIS; INSTABILITY; MECHANISMS; TOXICITY;
D O I：
10.1016/j.bmc.2023.117580
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We here report a new molecule DoNA binding to a CAG repeat RNA. DoNA is a dimer of the NA molecule that we previously reported. NA binds with high affinity to a CAG repeat DNA but not significantly to a CAG repeat RNA. Binding analyses using SPR and CSI-TOF MS indicated a significant increase in the affinity of DoNA to a single stranded CAG repeat RNA compared to NA. Systematic investigation of the RNA motifs bound by DoNA using hairpin RNA models revealed that DoNA binds to the CAG units at overhang and terminal positions, and notably, it binds to the structurally flexible internal and hairpin loop region.
引用
收藏
页数：6
相关论文
共 50 条
  • [41] R-SIM: A Database of Binding Affinities for RNA-small Molecule Interactions
    Krishnan, Sowmya Ramaswamy
    Roy, Arijit
    Gromiha, M. Michael
    JOURNAL OF MOLECULAR BIOLOGY, 2023, 435 (14)
  • [42] An interpretable deep learning model predicts RNA-small molecule binding sites
    Xi, Wenyu
    Wang, Ruheng
    Wang, Li
    Ye, Xiucai
    Liu, Mingyang
    Sakurai, Tetsuya
    FUTURE GENERATION COMPUTER SYSTEMS-THE INTERNATIONAL JOURNAL OF ESCIENCE, 2024, 159 : 557 - 566
  • [43] Augmented base pairing networks encode RNA-small molecule binding preferences
    Oliver, Carlos
    Mallet, Vincent
    Gendron, Roman Sarrazin
    Reinharz, Vladimir
    Hamilton, William L.
    Moitessier, Nicolas
    Waldispuhl, Jerome
    NUCLEIC ACIDS RESEARCH, 2020, 48 (14) : 7690 - 7699
  • [44] Efficient NMR Screening Approach to Discover Small Molecule Fragments Binding Structured RNA
    Shortridge, Matthew D.
    Varani, Gabriele
    ACS MEDICINAL CHEMISTRY LETTERS, 2021, 12 (08): : 1253 - 1260
  • [45] Sustained Epigenetic Reactivation in Fragile X Neurons with an RNA-Binding Small Molecule
    Kam, Christina W.
    Dumelie, Jason G.
    Ciceri, Gabriele
    Yang, Wang-Yong
    Disney, Matthew D.
    Studer, Lorenz
    Jaffrey, Samie R.
    GENES, 2025, 16 (03)
  • [46] Discovery of a self-assembling small molecule that sequesters RNA-binding proteins
    Kim, Hyoseok
    Cui, Changyi
    Toh, Kohei
    Ado, Genyir
    Ogawa, Tetsuya
    Zhang, Yixin
    Sato, Shin-ichi
    Lim, Yong-Beom
    Kurata, Hiroki
    Zhou, Lu
    Uesugi, Motonari
    CHINESE CHEMICAL LETTERS, 2025, 36 (05)
  • [47] Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila
    Shieh, Shin-Yi
    Bonini, Nancy M.
    HUMAN MOLECULAR GENETICS, 2011, 20 (24) : 4810 - 4821
  • [48] Reduction of Huntington's Disease RNA Foci by CAG Repeat-Targeting Reagents
    Urbanek, Martyna O.
    Fiszer, Agnieszka
    Krzyzosiak, Wlodzimierz J.
    FRONTIERS IN CELLULAR NEUROSCIENCE, 2017, 11
  • [49] SCAN™ - A High-Throughput Assay for Detecting Small Molecule Binding to RNA Targets
    Baugh, Chris
    Wang, Shaohui
    Li, Bin
    Appleman, James R.
    Thompson, Peggy A.
    JOURNAL OF BIOMOLECULAR SCREENING, 2009, 14 (03) : 219 - 229
  • [50] Rationally designed small molecules targeting toxic CAG repeat RNA that causes Huntington's disease (HD) and spinocerebellar ataxia (SCAs)
    Khan, Eshan
    Biswas, Soumen
    Mishra, Subodh Kumar
    Mishra, Ribhav
    Samanta, Sampak
    Mishra, Amit
    Tawani, Arpita
    Kumar, Amit
    BIOCHIMIE, 2019, 163 : 21 - 32
12345