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

页数：6

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