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Faculty of Medicine School of Medicine Department of Medical Sciences, Chemistry |
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Professor |
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Related SDGs |
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XU Yan
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Degree 【 display / non-display 】
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Doctor(Medicine) ( 2004.3 Tokyo Medical and Dental University )
Research Areas 【 display / non-display 】
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Nanotechnology/Materials / Chemical biology
Papers 【 display / non-display 】
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Solution structure of Z-form DNA bound to a curaxin ligand CBL0137 Reviewed International journal
Liu F., Wang S., Xu Y.
Nucleic Acids Research 54 ( 4 ) 2026.2
Authorship：Last author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Nucleic Acids Research
Z-DNA is known to be a left-handed alternative form of DNA and has important biological roles in cancer and other genetic diseases. In a recent study, we discovered CBL0137, a curaxin ligand, to enhance cancer immunotherapy by inducing Z-DNA formation and activating the Z-DNA-binding protein ZBP1. However, the structural information on binding complexes between Z-DNA and CBL0137 ligand has not reported to date. Here we present the first high-resolution structure of the complex between a Z-DNA and a curaxin ligand CBL0137. This compound is observed to interact with the Z-DNA through π-stacking and zig-zag localization. Furthermore, we directly observe the complex in living human cells using in-cell <sup>19</sup>F NMR for the first time. This structural information provides a platform for the design of topology-specific Z-DNA-targeting compounds and is valuable for the development of new potent anticancer drugs.
DOI： 10.1093/nar/gkag104
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Manipulating DNA and RNA structures via click-to-release caged nucleic acids for biological and biomedical applications Reviewed International journal
Wang S., Saneyoshi H., Xu P., Oguri N., Yamashita A., Xu Y.
Nucleic Acids Research 53 ( 12 ) 2025.7
Authorship：Last author, Corresponding author 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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Z-form DNA-RNA hybrid blocks DNA replication Reviewed International coauthorship International journal
Shiyu Wang, Yan Xu
Nucleic Acids Research 53 ( 5 ) 2025.3
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)
DOI： 10.1093/nar/gkaf135
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Synthesis of Oligonucleotide RNA Containing 2´-Deoxy-2´-Fluoroarabinoguanosine (2´F-araG) for Stabilization of the Human Telomeric RNA G-Quadruplex Reviewed International journal
Saneyoshi H., Iwakiri R., Wang S., Xu Y.
Current Protocols 6 ( 4 ) 2026.4
Authorship：Last author, Corresponding author 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 International journal
Saneyoshi H., Ishizuka T., Wang S., Iwakiri R., Xu Y.
Chemistry A European Journal 31 ( 39 ) 2025.7
Authorship：Last author, Corresponding 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.
Books 【 display / non-display 】
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Oligonucleotide Containing 8-Trifluoromethyl-2′-Deoxyguanosine as a Z-DNA Probe (Z-DNA) International journal
Hong-Liang Bao & Yan Xu（ Role： Contributor）
Methods in Molecular Biology 2023.3 （ ISBN:978-4065207864 ）
Language：English Book type：Scholarly book
Z-DNA structure is a noncanonical left-handed alternative form of DNA, which has been suggested to be biologically important and is related to several genetic diseases and cancer. Therefore, investigation of Z-DNA structure associated with biological events is of great importance to understanding the functions of these molecules. Here, we described the development of a trifluoromethyl labeled deoxyguanosine derivative and employed it as a 19F NMR probe to study Z-form DNA structure in vitro and in living cells.
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In Cell 19F NMR for G-quadruplex (Handbook of Chemical Biology of Nucleic Acids) International journal
Yan Xu（ Role： Contributor）
Springer, Singapore 2023.1 （ ISBN:978-981-16-1313-5 ）
Language：English Book type：Scholarly book
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核酸科学ハンドブック(第II部 核酸科学の最前線 3. グアニン四重鎖構造)
徐岩（ Role： Contributor , 第II部 核酸科学の最前線 3. グアニン四重鎖構造）
講談社 2020.12 （ ISBN:978-4065207864 ）
Total pages：576 Language：Japanese Book type：Scholarly book
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T. Ishizuka, H. L. Bao, Y. Xu*（ Role： Joint author）
Springer 2019.8
Total pages：pp 407-433 Language：English Book type：Scholarly book
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Clipping of Telomere from Human Chromosomes Using a Chemistry-Based Artificial Restriction DNA Cutter（共著）
Takumi Ishizuka, Yan Xu, Makoto Komiyama（ Role： Joint author）
John Wiley & Sons, Inc. 2015.6
Language：English
MISC 【 display / non-display 】
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Human telomere DNA / RNA G-quadruplex and cancer therapy development Invited
2020.4
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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Human Telomere RNA Structure and Function Reviewed
Y. Xu
Telomere and Telomerase 3 2016.11
Language：English Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
DOI： 10.14800/tt.1455
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化学の目で、ヒトテロメアの謎を解く(共著)
徐岩
日本化学会生体関連部会ニュースレター 26 ( 1 ) 3 - 6 2011.6
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (other) Publisher：日本化学会
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G-カルテット安定化分子でテロメラーゼを阻害する
Shinohara,K., Xu,Y., Sugiyama,H
化学 60 ( 7 ) 68 - 69 2005.7
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：化学同人
Presentations 【 display / non-display 】
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A click-to-release strategy in nucleic acids: manipulating DNA and RNA structures for biological and biomedical applications International conference
Shiyu Wang, Hisao Saneyoshi, Yan Xu
第52回国際核酸化学シンポジウム 2025.11.12
Event date： 2025.11.12 - 2025.11.14
Language：English Presentation type：Oral presentation (general)
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Solution structure of Z-form DNA bound to acuraxin ligand CBL0137 International conference
Feifan Liu, Shiyu Wang, Yan Xu
第52回国際核酸化学シンポジウム 2025.11.12
Event date： 2025.11.12 - 2025.11.14
Language：English Presentation type：Poster presentation
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Visualization of G-quadruplexes in animals and tissues International conference
Meng-Hao Jia, Yan Xu
第52回国際核酸化学シンポジウム 2025.11.13
Event date： 2025.11.12 - 2025.11.14
Language：English Presentation type：Poster presentation
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Fluorinated G-quadruplex RNA for Highly Sensitive Photodynamic Diagnosis International conference
Rie Iwakiri, Shiyu Wang, Takashi Okazoe, Mihoko Noro, Yan Xu
第52回国際核酸化学シンポジウム 2025.11.12
Event date： 2025.11.12 - 2025.11.14
Language：English Presentation type：Poster presentation
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3-Cyano-3-Deazaguanosine: Synthesis and Structural Basis for RNA Stabilization International conference
Hisao Saneyoshi, Shiyu Wang, Yan Xu
第52回国際核酸化学シンポジウム 2025.11.13
Event date： 2025.11.12 - 2025.11.14
Language：English Presentation type：Poster presentation
Awards 【 display / non-display 】
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宮崎大学ハイステップ研究者
2019.2 宮崎大学
徐岩
Award type：International academic award (Japan or overseas) Country：Japan
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光科学技術研究振興財団研究奨励金
2018.2 光科学技術研究振興財団
徐岩
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
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宮崎大学ハイステップ研究者
2016.12 宮崎大学
徐岩
Country：Japan
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武田科学振興財団研究奨励金
2013.8 武田科学振興財団
徐岩
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
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内藤記念科学振興財団研究奨励金
2011.12 内藤記念科学振興財団
徐岩
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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19F NMR分子技術の開発によるヒト細胞内DNA及びRNA高次構造の解明 International coauthorship
Grant number：21H02081 2021.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Principal investigator
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非標準型核酸の構造・機能及び蛋白質との相互作用の解明を目指したｹﾐｶﾙﾊﾞｲｵﾛｼﾞｰ
Grant number：24K01648 2024.04 - 2027.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Principal investigator
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クリック反応技術と軸配位子糖鎖連結ポリフィリン錯体を融合した革新的PDTの開発
Grant number：22K08806 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
七島 篤志、
Authorship：Coinvestigator(s)
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分子結合技術を用いた新たな造影剤による革新的がんMRI画像化技術の開発
Grant number：20K08000 2020.04 - 2023.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
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胆管癌の局所制御増強と光線過敏軽減による普及を目指した次世代光線力学的療法の開発
Grant number：19K09178 2019.04 - 2022.03
科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
Other research activities 【 display / non-display 】
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Advisory Board of Sci
2018.01
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Editorial Board of Molecules
2017.04
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"Faculty of 1000"のメンバー
2008.04
"Faculty of 1000" とは、生物学と医学研究の出版物において、最も重要だと思われる論文を認定し評価を与える国際学術組織です。
Available Technology 【 display / non-display 】
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生命分子機構を解明する革新的分子技術の開発
テロメアを標的とする革新的分子技術の開発
化学による革新的がん可視化診断技術の開発Home Page： 医学部機能制御学講座生命分子科学分野
Related fields where technical consultation is available：機能性核酸の創製、イメージング分子合成、細胞・動物分子イメージング、活性小分子の作製、短鎖ペプチドの合成
Message：・共同研究の希望テーマ：細胞・動物分子イメージング、人工核酸医薬、がん診断・治療