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Affiliation |
Faculty of Medicine School of Medicine Department of Medical Sciences, Chemistry |
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Associate Professor |
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Related SDGs |
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SANEYOSHI Hisao
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Research Areas 【 display / non-display 】
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Nanotechnology/Materials / Chemistry and chemical methodology of biomolecules / 核酸化学
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Nanotechnology/Materials / Synthetic organic chemistry / 核酸合成化学
Papers 【 display / non-display 】
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MRI tumor imaging by click chemistry using Gd(iii)-DOTA-DBCO and Ac(4)ManNAz. Reviewed
Ichiki N, Saneyoshi H, Satoh H, Nanashima A, Xu Y
RSC advances 16 ( 29 ) 26448 - 26451 2026.5
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Saneyoshi H., Iwakiri R., Wang S., Xu Y.
Current Protocols 6 ( 4 ) e70366 2026.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Current Protocols
This article provides detailed synthetic protocols for the preparation of RNA oligonucleotides containing 2′-deoxy-2′-fluoroarabinoguanosine (2′F-araG). Incorporation of this modification into a human telomeric RNA sequence stabilizes the G-quadruplex (G4) structure. We developed a convenient synthesis of 2′F-araG starting from commercially available 2-deoxy-2-fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofuranose. The resulting 2′F-araG was converted into the corresponding 3′-phosphoramidite via a routine three-step procedure. This phosphoramidite monomer was then used for automated solid-phase RNA oligonucleotide synthesis. Finally, the resulting 2′F-araG-modified RNA oligonucleotides were employed to identify the positions that most effectively stabilize the G4 structure. © 2026 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of 2´F-araG phosphoramidites. Basic Protocol 2: Preparation of 2´F-araG-modified RNA oligonucleotides. Basic Protocol 3: Evaluation of 2´F-araG stabilization of RNA G4 structure by circular dichroism spectroscopy.
DOI： 10.1002/cpz1.70366
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Effects of Fluorine Substitution on the Human Telomeric RNA G-Quadruplex Structure Reviewed
Saneyoshi H., Ishizuka T., Wang S., Iwakiri R., Xu Y.
Chemistry A European Journal 31 ( 39 ) e202501508 2025.7
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Chemistry A European Journal
DNA G-quadruplex structures can adopt different topologies, whereas RNA G4 predominantly forms parallel-type structures. While previous studies have reported the stabilization of DNA G-quadruplex topologies using syn-favored nucleosides, stabilization of parallel-type RNA G-quadruplexes through chemical modification remains unachieved. Here, we demonstrate that substitution with 2′-deoxy-2′-fluoroarabinoguanosine (2′F-araG) at specific positions in the human telomeric RNA sequence stabilizes the parallel-type G-quadruplex structure. This stabilization arises from electrostatic interactions via pseudo hydrogen bonds, induced by the 2′F-araG modification.
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Wang S., Saneyoshi H., Xu P., Oguri N., Yamashita A., Xu Y.
Nucleic Acids Research 53 ( 12 ) 2025.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Nucleic Acids Research
Effectively controlling the structures of DNA and RNA is crucial for their functional utilization in material development, biological regulation, and medical applications. Here, we present a gain-of-function strategy for controlling DNA and RNA structures using an inverse electron-demand Diels-Alder (IEDDA) based click-to-release reaction. By incorporating click reaction-cleavable caged moiety into oligonucleotides, we disrupt activated base pairs, allowing controlled release of biofunctional higher-order nucleic acid structures. This click-to-release caged DNA was employed to control DNA duplex formation. Next, we demonstrated the utility of "click-to-release"strategy for regulated release of Z-DNA or Z-RNA and bind associated proteins. In addition, the approach was used to manipulated G-quadruplex formation in vitro and in vivo, enabling visual detection of G-quadruplex using BVE-caged DNA with fluorescent dye. Furthermore, we demonstrated the utility of click-to-release caged DNA for Quantum Dots (QDs) functionalization, enabling precise molecular imaging for cancer diagnosis. Finally, we developed a click-to-release controllable nucleic acid aptamer for precise blood clotting regulation and anticoagulation therapy. This strategy provides moderate kinetics, excellent orthogonality, and biocompatibility. It establishes a new pathway towards control of nucleic acid structures and functions, which has promising applications in various biological procedures and nucleic acid medicines.
DOI： 10.1093/nar/gkaf571
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Unusual topological RNA G-quadruplex formed by an RNA duplex: implications for the dimerization of SARS-CoV-2 RNA Reviewed International coauthorship
Wang Shiyu, Song Yi, He Zhiyong, Saneyoshi Hisao, Iwakiri Rie, Xu Pengyu, Zhao Chuanqi, Qu Xiaogang, Xu Yan
Chemical Communications 59 ( 85 ) 12703 - 12706 2023.10
Language：English Publishing type：Research paper (scientific journal)
The infectious disease coronavirus 2019 (SARS-CoV-2) is caused by a virus that has RNA as its genetic material. To understand the detailed structural features of SARS-COV-2 RNA, we probed the RNA structure by NMR. Two RNA sequences form a duplex and self-associate to form a dimeric G-quadruplex. The FrG nucleoside was employed as a 19F sensor to confirm the RNA structure in cells by 19F NMR. A FRET assay further demonstrated that the dimeric G-quadruplex resulted in RNA dimerization in cells. These results provide the basis for the elucidation of SARS-COV-2 RNA function, which provides new insights into developing novel antiviral drugs against SARS-COV-2.
DOI： 10.1039/d3cc03192f
MISC 【 display / non-display 】
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新しい抗ウイルス薬の設計を目指して 非酵素的なヌクレオシド5′-モノリン酸への変換
實吉 尚郎
化学 75 ( 12 ) 63 2020.12
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
Grant-in-Aid for Scientific Research 【 display / non-display 】
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細胞内で機能する15N標識RNAグアニン四重鎖プローブの開発とIn-cell 15N-NMRへの応用
Grant number：25K08823 2025.04 - 2028.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
Authorship：Principal investigator
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がん細胞選択的な細胞死を誘導する合成核酸の開発
Grant number：22K05319 2022.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
實吉 尚郎
Authorship：Principal investigator
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Synthesis and characterization of metallo-DNA nanowire with infinite, uninterrupted one-dimensional metal ions array
Grant number：17H03033 2017.04 - 2021.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Authorship：Principal investigator
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細胞膜透過能を有する合成核酸の開発
Grant number：17K01966 2017.04 - 2020.03
日本学術振興会 科学研究費助成事業 基盤研究(C)
實吉 尚郎
Authorship：Principal investigator
本研究は、細胞膜透過能を有する合成核酸の開発を目指すものである。すなわち、核酸分子自体に細胞膜透過性を有機化学的に付与し、細胞内導入を劇的に簡便にする。細胞膜透過後、適切なトリガー（細胞内環境）によって保護基が除去され活性を示す合成核酸の創製を目指している。本年度は、昨年度に見出した保護基をモデル核酸医薬のプロドラッグ化へ応用した。得られたモデル分子の細胞内部での機能を検討した。細胞内への導入は、合成核酸を細胞へ直接添加する方法と導入剤（トランスフェクション試薬）を用いる一般的な方法を用いた。遺伝子の発現抑制を指標に、細胞内でどの程度機能しているかを評価した。導入剤を用いた場合、プロドラッグ型核酸は、親化合物（保護基が脱保護されている）と比較して高い活性が観測された。保護基の導入により細胞内での安定性が向上したためと推測している。直接添加の場合では、導入剤を使用した場合と比較してやや活性が低下した。親化合物と比較すると、より高い活性が観測された。これらの結果より、保護基を結合した効果を確認することができた。今後は、インキュベート時間、保護基の導入数や導入位置を最適化し、直接添加で機能する合成核酸を目指していきたい。