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Position |
Professor |
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Research Field |
Nanotechnology/Materials / Bio chemistry, Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Biofunction and bioprocess engineering, Nanotechnology/Materials / Nanomaterials |
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External Link |
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Graduating School 【 display / non-display 】
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Kyoto University Faculty of Science Graduated
- 1979.3
Graduate School 【 display / non-display 】
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Kyoto University Graduate School, Division of Natural Science Doctor's Course Completed
- 1985.3
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Kyoto University Graduate School, Division of Natural Science Master's Course Completed
- 1982.3
Campus Career 【 display / non-display 】
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KONAN UNIVERSITY Frontier Institute for Biomolecular Engineering Research, Konan University Distinguished Professor
2024.4
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KONAN UNIVERSITY Faculty of Frontiers of Innovative Research in Science and Technology Faculty of Frontiers of Innovative Research in Science and Technology Department of Nanobiochemistry Professor
2009.4 - 2024.3
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KONAN UNIVERSITY Frontier of Institute for Biomolecular Engineering Research in Science and Technology Department of Nanobiochemistry Director in General
2004.4 - 2024.3
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ハイテクリサーチセンター 所長
2001.4 - 2004.3
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KONAN UNIVERSITY Faculty of Science Professor
1994.4 - 2009.3
External Career 【 display / non-display 】
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学校法人 甲南学園
2012.8
Country：Japan
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ロチェスター大学
1985.4 - 1988.3
Country：United States
Papers 【 display / non-display 】
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Conformational Transition of Viral Nucleic Acids in a Capsid‐Like Confined Environment Reviewed International journal
Sunipa Sarkar, Hisae Tateishi‐Karimata, Kazunori Matsuura, Naoki Sugimoto
Chemistry – A European Journal 31 ( 45 ) e01208 - e01208 2025.7
Authorship：Corresponding author Publisher：Wiley
Abstract
Nucleic acid molecules within viral genomes can fold into noncanonical structures, such as G‐quadruplexes (G4s), which play crucial roles in regulating viral gene expression. These genomes are confined within capsid environments that vary in dimensions and ionic compositions. Structural transitions in RNA or DNA within these confined environments are essential for modulating viral biological functions; however, these transitions remain poorly understood. In this study, we demonstrated that an RNA sequence derived from the human immunodeficiency virus (HIV‐1) genome adopts a dynamic equilibrium between G4 and hairpin (Hp) structures modulated by ionic conditions. The equilibrium shifts toward the G4 conformation in the presence of potassium (K⁺) and magnesium (Mg<sup>2</sup>⁺) ions. Using reverse micelles (RMs) as mimetics of the intracapsid environment, we showed that the size of the RM water pool influences significantly this equilibrium: smaller water pools favor G4 formation, whereas larger pools prefer the Hp structure owing to variations in the dielectric constant. Notably, the addition of Mg<sup>2</sup>⁺ ions alters the size‐dependent effects of RMs by stabilizing the G4 structure. These findings highlight the critical roles of environmental confinement and ionic conditions in regulating viral RNA structural dynamics, offering new insights into RNA‐based regulatory mechanisms and their impact on viral gene expression. -
Twisting tetraplex DNA: A strand dynamics regulating i-motif function in diverse molecular crowding environments Reviewed International coauthorship International journal
Shuntaro Takahashi, Saptarshi Ghosh, Marko Trajkovski, Tatsuya Ohyama, Janez Plavec, Naoki Sugimoto
Nucleic Acids Research 53 ( 12 ) gkaf500 - gkaf500 2025.6
Authorship：Corresponding author Publisher：Oxford University Press (OUP)
Abstract
Intercalated motif (i-motif) tetraplex DNA plays a crucial role in gene expression and diseases. However, due to the limited number of i-motif binding proteins in human cells, the chemical mechanisms regulating i-motifs within cell remain currently unknown. Thus, molecular environment should have a main factor to control i-motif formation and functions in cells. Here, we systematically investigated the stability and functions of i-motif DNAs by using various polyethylene glycols (PEGs) and oligoethylene glycols (OEGs) that mimicked diverse cellular crowding environments. We found that the human telomere i-motif was significantly stabilized by PEGs and OEGs having six or more ethylene glycol units, whereas it was destabilized by those having less than six units. As these stabilization effects coincided with the drastic changes in hypochromicity by i-motif helixes, we quantitatively validated these effects through changes in solution properties and by assessing the twisting of the tetraplex structure using nuclear magnetic resonance (NMR) and molecular dynamics simulations. Furthermore, cosolute-induced twisting dynamics controlled by different cosolutes changed the activation energy barrier of replication by a twofold magnitude along the i-motif-forming DNAs. Our findings indicate that regulatory mechanisms underlying the biological roles of i-motifs across different cellular phases may exist by molecular environments.DOI： 10.1093/nar/gkaf500
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Controlling the local conformation of RNA G-quadruplex results in reduced RNA/peptide cytotoxic accumulation associated with C9orf72 ALS/FTD Reviewed International journal
Saki Matsumoto, Hisae Tateishi-Karimata, Tatsuya Ohyama, Naoki Sugimoto
Small Methods 9 ( 6 ) 2401630 - 2401630 2025.6
Authorship：Corresponding author
Abstract
Repeat expansion of d(G4C2) in the noncoding region of the C9orf72 gene contributes to neurodegenerative diseases. The repeat expansion transcript r(G4C2) induces RNA/peptide accumulation, which, in turn, induces cytotoxicity and accelerates the development of neurodegenerative diseases. Such cytotoxic accumulation is triggered by peptide aggregation. Here, a technique is developed to prevent accumulation by regulating RNA interactions, assuming that RNA structure is important for peptide interactions. A screening method is used to identify compounds that suppress RNA accumulation of r(G4C2) repeats. The four compounds are identified with wide π-planes containing hydroxyl, methoxy, and cyclic ether groups that suppressed RNA accumulation. Interestingly, these compounds also suppressed RNA/peptide accumulation in neuroblastoma cells, indicating that RNA accumulation is a key regulator of RNA/peptide cytotoxic aggregate formation. In vitro and in silico physicochemical analyses reveal that these compounds bind to the loop region of the G-quadruplex via hydrogen bonds or CH-π interactions, resulting in an altered loop conformation. Importantly, these conformational changes inhibited RNA G-quadruplex associations. These results show that conformational changes are promising for controlling the interactions between G-quadruplexes and further RNA accumulation. These findings may be useful in the development of therapeutic strategies for the treatment of neurodegenerative diseases.
Keywords: G‐quadruplex; RNA gelation; compound screening; liquid–liquid phase separation; neurodegenerative diseases. -
Predictability of environment-dependent formation of G-quadruplex DNAs in human mitochondria Reviewed
Lutan Liu;Shuntaro Takahashi;Sarptarshi Ghosh;Tamaki Endoh;Naoto Yoshinaga;Keiji Numata;Naoki Sugimoto
Communications Chemistry 8 ( 1 ) 135 - 135 2025.5
Authorship：Corresponding author
Abstract
Molecular crowding affects the stability of nucleic acids (DNA and RNA) and induces their non-canonical structures. As the level of molecular crowding varies spatio-temporally in cells, it would be beneficial to predict the behaviour of DNA and RNA structures depending on the local cellular environments. This has applications in human mitochondria, which possess an especially crowded condition. In this study, the predictability of guanine-quadruplex (G4) DNA formation in the environment specific to human mitochondria was investigated. In accordance with the stability of duplexes predicted by our nearest-neighbour parameters, the G-rich duplex stability was found to effectively decrease and G4 formation was induced in mitochondrion-like conditions compared to the nucleus-like conditions. Using a peptide-based mitochondrial targeting system, a G4 reporter assay performed in mitochondria indicated that G4 formation were more favoured in mitochondria more than in the nucleus. These findings provide insights useful for the prediction of the behaviour of nucleic acids in mitochondria. -
Imperfect G-quadruplex as an emerging candidate for transcriptional regulation Reviewed
Sunipa Sarkar, Hisae Tateishi-Karimata, Tatsuya Ohyama, Naoki Sugimoto
Nucleic Acids Res. 53 ( 5 ) gkaf164 - gkaf164 2025.2
Authorship：Corresponding author
Abstract
G-quadruplexes (G4s) with continuous G-tracts are well-established regulators of gene expression and important therapeutic targets for various diseases. However, bioinformatics analyses have identified G4-like sequences containing interrupted G-tracts, incorporating non-G nucleotides as bulges (buG4s). Our findings show that the stability of buG4s is significantly influenced by the bulge position and size within the G-tract, with bulges at the 5' end exhibiting the highest stability. Moreover, a molecular crowding condition inducing by poly (ethylene glycol), providing a suitable intracellular environment, stabilizes buG4s, especially those with longer bulges, making their formation more pronounced. A transcription assay performed under crowding conditions revealed that the transcription arrested efficiency by buG4s is affected not only by stability but also by the position and size of the bulge. Based on these findings, we propose a model for the preliminary screening of buG4 sequences according to their stability, distinguishing functional sequences capable of transcriptional arrest (ΔG°37 ≤ -3.3 kcal·mol-1) from nonfunctional sequences (ΔG°37 > -3.3 kcal·mol-1). This provides valuable insight into estimating the efficiency of target buG4 sequences in either arresting or facilitating transcription, presenting a novel approach and emphasizing buG4s as emerging therapeutic targets.DOI： 10.1093/nar/gkaf164
Books and Other Publications 【 display / non-display 】
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Stability Prediction of Canonical and Noncanonical Structures of Nucleic Acids.
S. Takahashi, H. Tateishi-Karimata, N. Sugimoto（ Role： Joint author）
Handbook of Chemical Biology of Nucleic Acids.Springer 2023
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Liquid Phase Separation and Nucleic Acids
H. Tateishi-Karimata, S. Matsumoto, N. Sugimoto（ Role： Joint author）
Handbook of Chemical Biology of Nucleic Acids.Springer 2023
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Effects of Molecular Crowding on Structures and Functions of Nucleic Acids.
T. Endoh, H. Tateishi-Karimata, N. Sugimoto（ Role： Joint author）
Handbook of Chemical Biology of Nucleic Acids.Springer 2023
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Chemistry and Biology of Non-canonical Nucleic Acids
N. Sugimoto（ Role： Sole author）
WILEY 2021.4
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相分離生物学の全貌（現代化学増刊46）
建石寿枝, 杉本直己（ Role： Joint author , 第Ⅳ部 生物学的相分離の理論）
東京化学同人 2021
Review Papers (Misc) 【 display / non-display 】
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分子夾雑系での核酸挙動
建石寿枝、三好大輔、杉本直己
CSJカレントレビュー「生体分環境の化学―分子夾雑と1分子で解き明かす生体の挙動―」化学同人 45 36 - 41 2023.2
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遺伝子発現における核酸の新機能 Reviewed
松本咲, 杉本直己
CSJカレントレビュー「進化を続ける核酸化学―ゲノム編集、非二重らせん、核酸医薬―」 41 146 - 154 2021.10
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細胞内の核酸物理化学 Reviewed
高橋俊太郎, 杉本直己
CSJカレントレビュー「進化を続ける核酸化学―ゲノム編集、非二重らせん、核酸医薬―」 41 14 - 21 2021.10
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フロントランナーに聞く「令和の時代も進化を続ける核酸化学」
神谷真子, 建石寿枝, 永次史, 山吉麻子, 杉本直己
CSJカレントレビュー「進化を続ける核酸化学―ゲノム編集、非二重らせん、核酸医薬―」 41 2 - 13 2021.10
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がん関連mRNAと光線力学療法
三好大輔, 杉本直己
CSJカレントレビュー「生体分子と疾患」 39 75 - 83 2021.8
Publisher：化学同人
Presentations 【 display / non-display 】
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“To B or not to B” in Nucleic Acids Chemistry Invited
N. Sugimoto
The Seminar of Beijing Advanced Center of RNA Biology(BEACON) (Beijing Advanced Center of RNA Biology(BEACON), Beijing) 2025.7 Beijing Advanced Center of RNA Biology(BEACON)
Event date： 2025.7
Country：China
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All about “To B or not to B” in Nucleic Acids Chemistr Invited
N. Sugimoto
The Seminar of University of Toronto 2025.7
Event date： 2025.7
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All About "To B or Not to B" in Nucleic Acids Chemistry Invited
N. Sugimoto
Gordon Research Conference (Nucleosides, Nucleotides and Oligonucleotides) (Salve Regina University, Newport) 2025.7 Gordon Research Conference
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“To B or not to B” in Nanotechnology of Nucleic Acid Invited
N. Sugimoto
The 12th Conference on DNA Nanotechnology (Jinniu Hotel, Chengdu ) 2025.6 Organizing Committee of the12th Conference on DNA Nanotechnology
Event date： 2025.6
Country：China
Nucleic acids (DNA and RNA) are genetic materials in living organisms and formed by a sequence of nucleobases. The stability of nucleic acids structures cannot be determined from only the sequence composition, as this property critically depends on the surrounding environment of the solution. The intracellular condition is greatly different from that of the diluted buffer typically used for standard experiments and is not constant in each local area of the cell. Thus, to make excellent nanomaterials with nucleic acids working in cells, stability predictions should reflect the situation under intracellular conditions and are required importantly. In this lecture, I will provide an overview of the basic concepts, methods, and applications of predicting the stabilities of nucleic acid structures. I explain the theory of the most successful prediction method based on a nearest-neighbor (NN) model. To improve the versality of prediction, corrections for various solution conditions considered hydration have been investigated.1-11 I also describe advances in the prediction of non-canonical structures of G-quadruplexes and i-motifs. Finally, studies of intracellular analysis and stability prediction are discussed for the application of NN parameters for human health and diseases.
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All about “To B or not to B” in Nucleic Acids Chemistry Invited
N. Sugimoto
XIXth Symposium on Chemistry of Nucleic Acid Components (SCNAC2025) (Hotel Ruze, Cesky Krumlov) 2025.6 Organizing committee of the 2025 SCNAC
Event date： 2025.6
Country：Czech Republic
Nucleic acids typically form a double helix structure through Watson-Crick base-pairing. In contrast, non-Watson-Crick base pairs can form other three-dimensional structures. Although it is well-known that Watson-Crick base pairs may be more unstable than non-Watson-Crick base pairs under some conditions, the importance of non-Watson-Crick base pairs has not been widely examined. Hoogsteen base pairs, which are one of the typical non-Watson-Crick base pairs, contain important hydrogen-bond patterns that form the helices of nucleic acids, such as in Watson-Crick base pairs, and can also form non-double helix structures such as triplexes and quadruplexes. In recent years, non-double helix structures have been discovered in cells and were reported to considerably influence gene expression. The complex behavior of these nucleic acids in cells is gradually being revealed, but the underlying mechanisms remain almost unknown. Quantitatively analyzing the structural stability of nucleic acids is important for understanding their behavior. A nucleic acid is an anionic biopolymer composed of a sugar, base, and phosphoric acid. The physicochemical factors that determine the stability of nucleic acid structures include those derived from the interactions of nucleic acid structures and those derived from the environments surrounding nucleic acids. The Gibbs free energy change (ΔG) of structure formation is the most commonly used physicochemical parameter for analyzing quantitative stability. Quantitatively understanding the intracellular behavior of nucleic acids involves describing the formation of nucleic acid structures and related reactions as ΔG. Based on this concept, we quantitatively analyzed the stability of double helix and non-double helix structures and found that decreased water activity, one of the important factors in crowded cellular conditions, significantly destabilize the formation of Watson-Crick base pairs but stabilizes Hoogsteen base pairs.
In my presentation, I will describe a physicochemical approach to understand the regulation of gene expressions based on the stability of nucleic acid structures (1). We developed new methods for predicting the stability of double and non-double helices in various molecular environments by mimicking intracellular environments. Furthermore, the physicochemical approach used for analyzing gene expression regulated by non-double helix structures is useful for not only determining how gene expression is controlled by cellular environments but also for developing new technologies to chemically regulate gene expression by targeting non-double helix structures such as G-quadruplexes and i-motifs. I will discuss the roles of Watson-Crick and Hoogsteen base pairs in cells based on our results and why both types of base pairing are required for life. Finally, a new concept in nucleic acid science beyond that of Watson and Crick base pairing is introduced.
Industrial property rights 【 display / non-display 】
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核酸の立体構造を制御する方法及びその用途、並びに、細胞内分子クラウディング環境を再現するための組成物
建石 寿枝、高橋 俊太郎、川内 敬子、杉本 直己
Application no：特願2022-189538
Other Research Activities 【 display / non-display 】
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私の自慢「知の系譜：挑戦するオストワルト・ギブスの末裔たち－物理化学は細胞の中へ，極限状態の生命へ」
2013.2
Book Review
Academic Awards Received 【 display / non-display 】
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The Ikehara Award (Top Award)
2024.9 Japan Society of Nucleic Acids Chemistry (JSNAC)
Naoki Sugimoto
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第72回日本化学会賞
2020.3 公益社団法人日本化学会 分子クラウディング環境における非二重らせん核酸の化学
杉本直己
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The Imbach-Townsend Award
2018.8 IS3NA（International Society for Nucleosides, Nucleotides, and Nucleic Acids）
N. Sugimoto
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Keynote Lecture賞
2016.6 European Chemistry Congress (Euro Chemistry2016)
Naoki Sugimoto
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第39回井植文化賞（科学技術部門）
2015.10 公益財団法人 井植記念会
杉本直己
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Quantitative prediction of nucleic acid structures and functions affected by spaciotemporal environmental factors in cells
2022.4 - 2027.3
JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research(S)
Authorship：Principal investigator
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イオンチャンネルは核酸の非二重らせん構造の形成と遺伝子発現を制御しているのか
2020.7 - 2022.3
JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Exploratory Research
イオンチャンネルは核酸の非二重らせん構造の形成と遺伝子発現を制御しているのか
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核小体内クラウディング環境におけるリボソームRNA形成の定量的解析
2019.11 - 2022.3
JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows
核小体内クラウディング環境におけるリボソームRNA形成の定量的解析
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核酸構造のトポロジーによる遺伝子発現の化学的制御
2019.4 - 2022.3
JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research(A)
杉本 直己
核酸構造のトポロジーによる遺伝子発現の化学的制御
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核酸の非二重らせん構造を調節し、がんの発症を制御するのは、カリウムイオンなのか
2018.4 - 2020.3
JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Exploratory Research
核酸の非二重らせん構造を調節し、がんの発症を制御するのは、カリウムイオンなのか
Other External funds procured 【 display / non-display 】
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ヒトがん遺伝子およびウイルス遺伝子を標的とした先制核酸医工学の開発～がん遺伝子の構造予測パラメータの開発～
2025.7 - 2026.3
公益財団法人 伊藤忠兵衛基金 医療研究助成金 公益財団法人伊藤忠兵衛基金医療研究助成金
杉本 直己
Authorship：principal_investigator
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非二重らせん核酸を活用した遺伝子発現の制御法を開発する核酸化学
2022.4 - 2027.3
日本学術振興会 研究拠点形成事業 学術国際交流事業
杉本 直己
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ヒトがん遺伝子およびウイルス遺伝子を標的とした先制核酸医工学の開発～がん遺伝子の構造予測パラメータの開発～
2022.4 - 2026.3
公益財団法人 伊藤忠兵衛基金 医療研究助成金 公益財団法人伊藤忠兵衛基金医療研究助成金
杉本 直己
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核酸の非標準構造を標的とした細胞応答の化学的制御技術の構築と先制核酸医
2014.4 - 2019.3
文部科学省 文部科学省私立大学戦略的研究基盤形成支援事業
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特異なmRNA構造を活用した翻訳フレームシフト及び産生タンパク質機能の制御
2013.4 - 2014.3
公益財団法人長瀬科学技術振興財団 長瀬科学技術振興財団助成金
Joint and Contract research activities (Public) 【 display / non-display 】
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フタロシアニンなどのπ共役化合物による細胞毒性検討および癌関連酵素の新規測定技術の開発
Domestic Joint Research
2011.4 - 2012.3
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平成23年度調査研究「生命科学分野に関する学術動向の調査研究」
General funded research
2011.4 - 2012.3
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DNAの高次構造に注目した細胞のがん化機構の解明と化学物質のリスク評価システムの構築
General funded research
2010.9 - 2011.8
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フタロシアニンなどのπ共役化合物の抗腫瘍効果の検討および生体センシングへの応用検討
Joint Research on Campus
2010.4 - 2011.3
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DNAの高次構造に注目した細胞のがん化機構の解明と化学物質のリスク評価システムの構築
General funded research
2009.9 - 2010.8
Preferred joint research theme 【 display / non-display 】
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生命分子(核酸・タンパク質等)の立体構造の解明
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生命分子間相互作用のデータベース化
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生命分子(核酸・タンパク質等)の物性解析
Committee Memberships 【 display / non-display 】
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2017.11 - 2020.8 日本核酸化学会 会長
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2015.5 - 2017.5 日本化学会 理事
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2013.3 - 2015.2 日本化学会 生体機能関連部会監事
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2011.3 - 2013.2 日本化学会 生体機能関連部会部会長
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2010.4 - 2017.3 社団法人 日本学術振興会 学術システム研究センター専門研究員
Social Activities 【 display / non-display 】
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ひょうご経済・雇用活性化プラン策定会議構成員
2018.6 - 2019.3
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ひょうご次世代産業高度化プロジェクト推進協議会委員
2018.4 - 2021.3
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南開大学客座教授
2017.3
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兵庫県ひょうご経済・雇用活性化プラン推進会議構成員
2016.7 - 2017.3