2021/10/21 更新

写真a

アマイケ カズマ
天池 一真
AMAIKE Kazuma
所属
物質科学国際研究センター 助教
大学院担当
大学院理学研究科
職名
助教
外部リンク

学位 1

  1. 博士(理学) ( 2016年3月   名古屋大学 ) 

 

論文 15

  1. Photopharmacological Manipulation of Mammalian CRY1 for Regulation of the Circadian Clock

    Kolarski Dusan, Miller Simon, Oshima Tsuyoshi, Nagai Yoshiko, Aoki Yugo, Kobauri Piermichele, Srivastava Ashutosh, Sugiyama Akiko, Amaike Kazuma, Sato Ayato, Tama Florence, Szymanski Wiktor, Feringa Ben L., Itami Kenichiro, Hirota Tsuyoshi

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   143 巻 ( 4 ) 頁: 2078 - 2087   2021年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of the American Chemical Society  

    CRY1 and CRY2 proteins are highly conserved components of the circadian clock that controls daily physiological rhythms. Disruption of CRY functions are related to many diseases, including circadian sleep phase disorder. Development of isoform-selective and spatiotemporally controllable tools will facilitate the understanding of shared and distinct functions of CRY1 and CRY2. Here, we developed CRY1-selective compounds that enable light-dependent manipulation of the circadian clock. From phenotypic chemical screening in human cells, we identified benzophenone derivatives that lengthened the circadian period. These compounds selectively interacted with the CRY1 photolyase homology region, resulting in activation of CRY1 but not CRY2. The benzophenone moiety rearranged a CRY1 region called the "lid loop"located outside of the compound-binding pocket and formed a unique interaction with Phe409 in the lid loop. Manipulation of this key interaction was achieved by rationally designed replacement of the benzophenone with a switchable azobenzene moiety whose cis-trans isomerization can be controlled by light. The metastable cis form exhibited sufficiently high half-life in aqueous solutions and structurally mimicked the benzophenone unit, enabling reversible period regulation over days by cellular irradiation with visible light. This study revealed an unprecedented role of the lid loop in CRY-compound interaction and paves the way for spatiotemporal regulation of CRY1 activity by photopharmacology for molecular understanding of CRY1-dependent functions in health and disease.

    DOI: 10.1021/jacs.0c12280

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  2. An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals

    Miller Simon, Aikawa Yoshiki, Sugiyama Akiko, Nagai Yoshiko, Hara Aya, Oshima Tsuyoshi, Amaike Kazuma, Kay Steve A., Itami Kenichiro, Hirota Tsuyoshi

    CELL CHEMICAL BIOLOGY   27 巻 ( 9 ) 頁: 1192 - +   2020年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cell Chemical Biology  

    Cryptochrome 1 (CRY1) and CRY2 are core regulators of the circadian clock, and the development of isoform-selective modulators is important for the elucidation of their redundant and distinct functions. Here, we report the identification and functional characterization of a small-molecule modulator of the mammalian circadian clock that selectively controls CRY1. Cell-based circadian chemical screening identified a thienopyrimidine derivative KL201 that lengthened the period of circadian rhythms in cells and tissues. Functional assays revealed stabilization of CRY1 but not CRY2 by KL201. A structure-activity relationship study of KL201 derivatives in combination with X-ray crystallography of the CRY1-KL201 complex uncovered critical sites and interactions required for CRY1 regulation. KL201 bound to CRY1 in overlap with FBXL3, a subunit of ubiquitin ligase complex, and the effect of KL201 was blunted by knockdown of FBXL3. KL201 will facilitate isoform-selective regulation of CRY1 to accelerate chronobiology research and therapeutics against clock-related diseases.

    DOI: 10.1016/j.chembiol.2020.05.008

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  3. Small Molecules Modulating Mammalian Biological Clocks: Exciting New Opportunities for Synthetic Chemistry

    Amaike Kazuma, Oshima Tsuyoshi, Skoulding Nicola Stephanie, Toyama Yoshifumi, Hirota Tsuyoshi, Itami Kenichiro

    CHEM   6 巻 ( 9 ) 頁: 2186 - 2198   2020年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Chem  

    Challenges and opportunities: • Increasing opportunities for the discovery of new circadian clock modulators, which are attractive drug candidates for clock-related diseases in pharmaceutical industry, and to enhance crop yield in agriculture. • Development of new reactions for rapid access to hit compound derivatives, accelerating structure-activity relationship studies, which are generally time consuming. • New approaches for target identification of clock-modulating small molecules, which is still challenging, enable molecular-level understanding and new structural designs.

    DOI: 10.1016/j.chempr.2020.08.011

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  4. Construction of a Fluorescent Screening System of Allosteric Modulators for the GABA(A) Receptor Using a Turn-On Probe 査読有り

    Sakamoto Seiji, Yamaura Kei, Numata Tomohiro, Harada Fumio, Amaike Kazuma, Inoue Ryuji, Kiyonaka Shigeki, Hamachi Itaru

    ACS CENTRAL SCIENCE   5 巻 ( 9 ) 頁: 1541 - 1553   2019年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS Central Science  

    γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The fast inhibitory actions of GABA are mainly mediated by GABAA receptors (GABAARs), which are widely recognized as clinically relevant drug targets. However, it remains difficult to create screening systems for drug candidates that act on GABAARs because of the existence of multiple ligand-binding sites and the delicate pentameric structures of GABAARs. We here developed the first turn-on fluorescent imaging probe for GABAARs, which can be used to quantitatively evaluate ligand-receptor interactions under live cell conditions. Using noncovalent labeling of GABAARs with this turn-on probe, a new imaging-based ligand assay system, which allows discovery of positive allosteric modulators (PAMs) for the GABAAR, was successfully constructed. Our system is applicable to high-throughput ligand screening, and we discovered new small molecules that function as PAMs for GABAARs. These results highlight the power of the use of a turn-on fluorescent probe to screen drugs for complicated membrane proteins that cannot be addressed by conventional methods.

    DOI: 10.1021/acscentsci.9b00539

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  5. Recognition-driven chemical labeling of endogenous proteins in multi-molecular crowding in live cells. 査読有り

    Amaike K, Tamura T, Hamachi I

    Chemical communications (Cambridge, England)   53 巻 ( 88 ) 頁: 11972 - 11983   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/c7cc07177a

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  6. Affinity-Guided Oxime Chemistry for Selective Protein Acylation in Live Tissue Systems. 査読有り

    Tamura T, Song Z, Amaike K, Lee S, Yin S, Kiyonaka S, Hamachi I

    Journal of the American Chemical Society   139 巻 ( 40 ) 頁: 14181 - 14191   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/jacs.7b07339

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  7. Synthesis of multiply arylated pyridines 査読有り

    Asako Takashi, Hayashi Wakana, Amaike Kazuma, Suzuki Shin, Itami Kenichiro, Muto Kei, Yamaguchi Junichiro

    TETRAHEDRON   73 巻 ( 26 ) 頁: 3669 - 3676   2017年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Tetrahedron  

    We have achieved a synthesis of multiply arylated pyridines by using a [4 + 2] cycloaddition of 2,4-diaryl-5-chloroxazoles and cinnamic acids as a key reaction. The resulting hydroxytriarylpyridines can be derivatized into triarylpyridines, tetraarylpyridines and pentaarylpyridines by sequential cross-couplings. This synthetic method allows for facile and rapid access to highly arylated pyridines with different aryl substituents.

    DOI: 10.1016/j.tet.2017.03.095

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  8. Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C-H Arylation/Ring-Transformation Strategy 査読有り

    Amaike Kazuma, Itami Kenichiro, Yamaguchi Junichiro

    CHEMISTRY-A EUROPEAN JOURNAL   22 巻 ( 13 ) 頁: 4384 - 4388   2016年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Chemistry - A European Journal  

    We have described a C-H arylation/ring-transformation strategy for the synthesis of triarylpyridines, which form the core structure of thiopeptide antibiotics. This synthetic method readily gave 2,3,6-triarylpyridines in a regioselective manner by a two-phase approach: C-H arylation (a nickel-catalyzed decarbonylative Suzuki-Miyaura cross-coupling and decarbonylative C-H coupling for the synthesis of 2,4-diaryloxazoles) and ring transformation ([4+2] cycloaddition of 2,4-diaryloxazoles with (hetero)arylacrylic acids). To showcase these methods, we have accomplished the formal synthesis of thiopeptide antibiotics GE2270 s and amythiamicins.

    DOI: 10.1002/chem.201600351

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  9. Direct C7 Functionalization of Tryptophan. Synthesis of Methyl (<i>S</i>)-2-((<i>tert</i>-Butoxycarbonyl)amino)-3-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1<i>H</i>-indol-3-yl)propanoate. 査読有り

    Amaike K, Loach RP, Movassaghi M

    Organic syntheses; an annual publication of satisfactory methods for the preparation of organic chemicals   92 巻   頁: 373 - 385   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.15227/orgsyn.092.0373

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  10. C7-derivatization of C3-alkylindoles including tryptophans and tryptamines. 査読有り

    Loach RP, Fenton OS, Amaike K, Siegel DS, Ozkal E, Movassaghi M

    The Journal of organic chemistry   79 巻 ( 22 ) 頁: 11254 - 63   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/jo502062z

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  11. beta-Selective C-H Arylation of Pyrroles Leading to Concise Syntheses of Lamellarins C and I 査読有り

    Ueda Kirika, Amaike Kazuma, Maceiczyk Richard M., Itami Kenichiro, Yamaguchi Junichiro

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   136 巻 ( 38 ) 頁: 13226 - 13232   2014年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of the American Chemical Society  

    The first general β-selective C-H arylation of pyrroles has been developed by using a rhodium catalyst. This C-H arylation reaction, which is retrosynthetically straightforward but results in unusual regioselectivity, could result in de novo syntheses of pyrrole-derived natural products and pharmaceuticals. As such, we have successfully synthesized polycyclic marine pyrrole alkaloids, lamellarins C and I, by using this β-selective arylation of pyrroles with aryl iodides (C-H/C-I coupling) and a new double C-H/C-H coupling as key steps.

    DOI: 10.1021/ja508449y

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  12. Late-Stage C-H Coupling Enables Rapid Identification of HDAC Inhibitors: Synthesis and Evaluation of NCH-31 Analogues 査読有り

    Sekizawa Hiromi, Amaike Kazuma, Itoh Yukihiro, Suzuki Takayoshi, Itami Kenichiro, Yamaguchi Junichiro

    ACS MEDICINAL CHEMISTRY LETTERS   5 巻 ( 5 ) 頁: 582 - 586   2014年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACS Medicinal Chemistry Letters  

    We previously reported the discovery of NCH-31, a potent histone deacetylase (HDAC) inhibitor. By utilizing our C-H coupling reaction, we rapidly synthesized 16 analogues (IYS-1 through IYS-15 and IYS-Me) of NCH-31 with different aryl groups at the C4-position of 2-aminothiazole core of NCH-31. Subsequent biological testing of these derivatives revealed that 3-fluorophenyl (IYS-10) and 4-fluorophenyl (IYS-15) derivatives act as potent pan-HDAC inhibitor. Additionally, 4-methylphenyl (IYS-1) and 3-fluoro-4-methylphenyl (IYS-14) derivatives acted as HDAC6-insensitive inhibitors. The present work clearly shows the power of the late-stage C-H coupling approach to rapidly identify novel and highly active/selective biofunctional molecules. © 2014 American Chemical Society.

    DOI: 10.1021/ml500024s

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  13. Nickel-Catalyzed Direct Coupling of Heteroarenes

    Yamaguchi Junichiro, Muto Kei, Amaike Kazuma, Yamamoto Takuya, Itami Kenichiro

    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN   71 巻 ( 6 ) 頁: 576 - 587   2013年6月

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    記述言語:日本語  

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  14. Nickel-catalyzed direct coupling of heteroarenes 査読有り

    Yamaguchi J., Muto K., Amaike K., Yamamoto T., Itami K.

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   71 巻 ( 6 ) 頁: 576 - 587   2013年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry  

    Nickel-catalyzed cross-coupling reactions have recently been receiving significant attention from the synthetic community as a way to construct carbon-carbon or carbon-heteroatom bonds, because nickel catalysts are less expensive and less toxic than palladium catalysts. We herein describe our recent developments in nickel-catalyzed biaryl coupling methodology, along with mechanistic studies and applications to the synthesis of natural products and pharmaceuticals. In particular, we focus on nickel-catalyzed direct coupling reactions in which "unreactive" bonds such as C-H, C-O, and C-C bonds are converted into biaryl moieties.

    DOI: 10.5059/YUKIGOSEIKYOKAISHI.71.576

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  15. Decarbonylative C-H Coupling of Azoles and Aryl Esters: Unprecedented Nickel Catalysis and Application to the Synthesis of Muscoride A 査読有り

    Amaike Kazuma, Muto Kei, Yamaguchi Junichiro, Itami Kenichiro

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   134 巻 ( 33 ) 頁: 13573 - 13576   2012年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of the American Chemical Society  

    A nickel-catalyzed decarbonylative C-H biaryl coupling of azoles and aryl esters is described. The newly developed catalytic system does not require the use of expensive metal catalysts or silver- or copper-based stoichiometric oxidants. We have successfully applied this new C-H arylation reaction to a convergent formal synthesis of muscoride A. © 2012 American Chemical Society.

    DOI: 10.1021/ja306062c

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▼全件表示

MISC 1

  1. Synthesis of Natural Products and Pharmaceuticals via Catalytic C-H Functionalization

    Yamaguchi J., Amaike K., Itami K.  

    Transition Metal-Catalyzed Heterocycle Synthesis via C-H Activation   頁: 505 - 550   2016年1月

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    記述言語:英語   出版者・発行元:Transition Metal-Catalyzed Heterocycle Synthesis via C-H Activation  

    The synthesis of natural products and pharmaceuticals, particularly those containing heterocyclic frameworks, can be dramatically simplified by using catalytic C-H functionalization. C-H functionalization has gathered significant interest from the organic synthesis community because it provides a new strategy to construct carbon-carbon and carbon-heteroatom bonds in highly functionalized, complex molecules without prefunctionalization. In this book chapter, methods in heterocycle substitution and synthesis using catalytic C-H functionalization are classified by heterocycle, with specific focus on the cutting-edge synthesis of natural products and pharmaceuticals.

    DOI: 10.1002/9783527691920.ch16

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科研費 2

  1. シナジー効果を有する化合物群のAI による探索と設計

    研究課題/研究課題番号:20H05797  2020年10月 - 2023年3月

    科学研究費助成事業  学術変革領域研究(B)

    山西 芳裕, 天池 一真, 竹下 潤一

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    担当区分:研究分担者 

    複数の薬剤の組み合わせによる相乗効果(薬剤シナジー)を活用した化学療法が、がんや神経変性疾患など多因子疾患に対する有効な治療法として注目されている。本研究では、疾患状態の生体情報を入力とし、シナジー効果を有する薬剤群を予測するAIを開発する。さらに、より高いシナジー効果を有する新しい化合物群を設計するAIを開発する。有機化合物の組み合わせ数は膨大であり、実験的に全ての可能性を検証することは不可能である。生体情報から複数の薬剤群(または化合物群)を最適化できないか?という問いに対し、物質・生命科学のビッグデータと情報科学のAI技術を融合し、新たな方法論を創生する。

  2. フェアリー化合物の科学とその応用展開

    研究課題/研究課題番号:20H05620  2020年7月 - 2025年3月

    科学研究費助成事業  特別推進研究

    河岸 洋和, 菅 敏幸, 鈴木 智大, 野村 崇人, 謝 肖男, 室井 誠, 高橋 公咲, 一家 崇志, 伊藤 英人, 天池 一真

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    担当区分:研究分担者 

    芝が輪状に周囲より繁茂あるいは枯死した後にキノコが発生する現象を「フェアリーリング」という。研究代表者はこの現象の原因物質(AHX,ICA,AOH)を発見した。その後,これら3物質(フェアリー化合物,fairy chemicalsと総称,FCsと略称)の植物における内生が判明し,さらに圃場試験において農作物の増収効果を示した。本研究では,植物と菌類中で新規な経路でこれらの物質が生合成されることを明らかにし,活性発現分子機構を解明する。また,農業への実用化を目指しFCsの作物の栽培実験での効果と作用機構を検討する。最終的にはFCsが新しい植物ホルモンであることを証明する。