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RNA干渉はその配列特異的な遺伝子発現抑制効果から、これまでに治療が困難であった病気への治療法として期待されているが、RNAの生体内不安定性がその妨げになっていました。 その問題を克服するために、私たちはRNAのナノ構造と生物活性の相関に注目しました。これまでに、図１に示すダンベル型ナノサークル構造を有するRNAデザインが、 天然RNA分子を生体内で安定化させ、かつ長期的なRNA干渉効果を有することを見出しました。本発見を契機として二本鎖環状RNAや分岐型RNAなどの様々な新規ナノ構造体を設計・構築し 、蛋白質翻訳や遺伝子発現抑制現象を見いだし、独自のRNAナノテクノロジー研究を展開している。

図3　環状RNAを用いた終わりのない回転式たんぱく質翻訳

通常のたんぱく質翻訳は開始コドンに始まり、ストップコドンに終わります。一方、ストップコドンを除いた環状RNAを用いてたんぱく質翻訳を行うと、終わりがないため原理的には永久にタンパク質合成が起こることになります。我々はこの「終わりのない回転式たんぱく質翻訳」現象がたんぱく質合成の効率を飛躍的に高めることを見出しました。詳しくはこのリンクをご参照ください。

参考文献

1. Hideto Maruyama, Yuko Nakashima, Satoshi Shuto, Akira Matsuda, Yoshihiro Ito, Hiroshi Abe
   Intracellular buildup reaction of active siRNA species from short RNA fragments
   Chemical Communications accepted (2013).
2. Naoko Abe, Michio Hiroshima, Hideto Maruyama, Yuko Nakashima, Yukiko Nakano, Akira Matsuda, Yasushi Sako, Yoshihiro Ito*, and Hiroshi Abe*
   Rolling circle amplification in a prokaryotic translation system using small circular RNA
   Angewandte Chemie International Edition,, 52(27), 7004-7008 (2013).
3. 阿部洋、阿部奈保子、柴田綾、伊藤嘉浩,
   「ナノ構造を制御したＲＮＡを用いたＲＮＡ干渉法」、
   アンチセンスDNA/RNA研究会誌 page 3, Vol.16, No.2, November 2012
4. Naoko Abe, Hiroshi Abe, Yoshihiro Ito
   Synthesis of Dumbbell-Shaped Cyclic RNAs for RNA Interference.
   Current Protocol Nucleic Acid Chemistry, 48:16.4.1-16.4.11 (2012)
5. Naoko Abe, Hiroshi Abe*, Chisato Nagai, Mitsuru Harada, Hiroto Hatakeyama, Hideyoshi Harashima, Takahito Ohshiro, Mizuki Nishihara, KazuhiroFurukawa, Mizuo Maeda, Satoshi Tsuneda, Yoshihiro Ito*
   Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference.
   Bioconjugate Chemistr, 22(10), 2082-2092, (2011).
6. Yuko Nakashima, Hiroshi Abe*, Naoko Abe, Kyoko Aikawa, Yoshihiro Ito*
   Branched RNA Nanostructures for RNA Interference.
   Chemical Communication, 47, 8367-8369 (2011).
7. Naoko Abe, Hiroshi Abe*, Takahito Ohshiro, Yuko Nakashima, Mizuo Maeda, Yoshihiro Ito*
   Synthesis and Characterization of Small Circular Double-Stranded RNAs.
   Chemical Communications, 47, 2125-2127 (2011).
8. Naoko Abe, Hiroshi Abe*, Yoshiiro Ito*
   Dumbbell-shaped nanocircular RNAs for RNA interference.
   Journal of the American Chemical Society, 129, 15108-15109 (2007).

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図１　RNAイメージング法：　RNA研究における基礎と応用

これまでに生細胞内RNAの存在を可視化・検出するための確立された方法はなかった。私たちのグループは、図１に示す独自に化学反応（求核置換反応や還元反応）に基づいて 蛍光発光する人口核酸プローブを開発し、細胞内RNAの定量的イメージング解析に成功した。本法の最大の特徴は、細胞内で化学的なシグナル増幅反応を起こすことにより、高感度な検出を可能とする点にある。

図２　ＲＮＡスプライシングの解析法：　診断・創薬へのアプローチ

本プローブを用いて、スプライシング反応のリアルタイム解析や世界で初めてのイントロン由来のラリアットRNAの直接検出に成功した（図２）。 　フローサイトメーターを用いた細胞内RNAの定量解析にも成功している（図3）。

図３　フローサイトメーターを用いた生細胞内ＲＮＡを定量解析

参考文献

1. Aya Shibata, Takanori Uzawa, Yuko Nakashima, Mika Ito, Yukiko Nakano, Satoshi Shuto, Yoshihiro Ito, and Hirosi Abe
   Very rapid DNA templated reaction for efficient signal amplification and its steady-state kinetic analysis of the turnover cycle
   Journal of the American Chemical Society, 135 (38), 14172−14178 (2013).
2. Hisao Saneyoshi Yoshihiro Ito, Hiroshi Abe
   Long-lived luminogenic probe for detection of RNA in a crude solution of living bacterial cells
   Journal of the American Chemical Society, 135 (37), 13632–13635 (2013).
3. Aya Shibata, Yoshihiro Ito, Hiroshi Abe*
   RNA-templated molecule release induced protein expression in bacterial cells.
   Chemical Communication, DOI: 10.1039/C2CC37826D, in press (2013).
4. Yasutsugu Tamura, Kazuhiro Furukawa, Rei Yoshimoto, Yuto Kawai, Minoru Yoshida, Satoshi Tsuneda, Yoshihiro Ito*, Hiroshi Abe*
   Detection of Pre-mRNA Splicing in vitro by an RNA-Templated Fluorogenic Reaction.
   Bioorganic Medicinal Chemistry Letters, 22(23), 7248-7251 (2012).
5. Aya Shibata, Hiroshi Abe*, Yoshihiro Ito
   Oligonucleotide-Templated Reactions for Sensing Nucleic Acids.
   Molecules, 17(3), 2446-2463 (2012).
6. Kazuhiro Furukawa, Hiroshi Abe*, Yasutsugu Tamura, Rei Yoshimoto, Minoru Yoshida, Satoshi Tsuneda, Yoshihiro Ito*
   Fluorescent Detection of Intron Lariat RNAs with Reduction-Triggered Fluorescence Probes.
   Angewandte Chemie International Edition, 50(50), 12020-12023, (2011).
7. Kazuhiro Furukawa, Hiroshi Abe*, Satoshi Tsuneda, Yoshihiro Ito*
   Photoactivatable fluorescein derivatives with azidomethyl caging groups for tracing oligonucleotides in living human cells.
   Organic Biomolecular Chemistry, 8, 2309-2311 (2010).
8. Aya Shibata, Hiroshi Abe*, Mika Ito, Yuko Kondo, Shigeru Shimizu, Kyoko Aikawa, Yoshihiro Ito*
   DNA templated nucleophilic aromatic substitution reactions for fluorogenic sensing of oligonucleotides.
   Chemical Communications, 43, 6586-6588 (2009).
9. Aya Shibata, Hiroshi Abe*, Kazuhiro Furukawa, Satoshi Tsuneda, Yoshihiro Ito*
   Reduction-triggered fluorescence probe for peptide-templated reactions.
   Chemical Pharmaceutical Bulletin, 57, 1223-1226 (2009).
10. Kazuhiro Furukawa, Hiroshi Abe*, Kayoko Hibino, Yasushi Sako, Satoshi Tsuneda, Yoshihiro Ito*
    Reduction-triggered Fluorescent Amplification Probe for Detection of endogenous RNAs in Living Human Cells.
    Bioconjugate Chemistry, 20, 1026?1036 (2009).
11. Kazuhiro Furukawa, Hiroshi Abe*, Jin Wang, Miwako Uda, Satoshi Tsuneda, Yoshihiro Ito*
    Reduction-triggered red fluorescent probes for dual-color detection of oligonucleotide sequences.
    Organic Biomolecular Chemistry, 7, 671-677 (2009).
12. Kazuhiro Frukawa, Hiroshi Abe*, Naoko Abe, Mitsuru Harada, Satoshi Tsuneda, Yoshihiro Ito*
    Fluorescence generation from tandem repeats of a malachite green RNA aptamer using rolling circle transcription.
    Bioorganic Medicinal Chemistry Letters, 18, 4562-4565 (2008)
13. Hiroshi Abe*, Jin Wang, Kazuhiro Furukawa, Kazuma Oki, Miwako Uda, Satoshi Tsuneda, Yoshihiro Ito*
    A reduction-triggered fluorescence probe for sensing nucleic acids.
    Bioconjugate Chemistry, 19, 1219-1226 (2008).
14. Adam P. Silverman, Hiroshi Abe, Eric T. Kool*
    Quenched autoligation probes.
    Methods in Molecular Biology, 429, 161-170 (2008).
15. Mingze Liu, Hiroshi Jinmei, Hiroshi Abe*, Yoshihiro Ito*
    Chemical aminoacylation of RNA by an intermolecular adenosine transfer reaction.
    Chemistry Letters, 37, 102-103 (2008).
16. Hiroshi Abe*, Yuko Kondo, Hiroshi Jinmei, Naoko Abe, Kazuhiro Furukawa, Atsushi Uchiyama, Satoshi Tsuneda, Kyoko Aikawa, Isamu Matsumoto, Yoshihiro Ito*
    Rapid DNA chemical ligation for amplification of RNA and DNA signal.
    Bioconjugate Chemistry, 19, 327-333 (2008).
17. Hiroshi Abe, Eric T. Kool*
    Flow cytometric detection of specific RNAs in native human cells with quenched auto ligating FRET probes.
    Proceedings of the National Academy of Sciences of the United States of America, 103, 263-268 (2006).
18. Hiroshi Abe, Eric T. Kool*
    Destabilizing Universal Linkers for Signal Amplification in Self-Ligating Probes for RNA.
    Journal of the American Chemical Society, 126, 43, 13980-13986 (2004).
19. Sinsuke Sando, Hiroshi Abe, Eric T. Kool*
    Quenched auto-Ligating DNAs: Multicolor identification of Nucleic Acids at Single Nucleotide Resolution.
    Journal of the American Chemical Society, 126, (4), 1081-1087 (2004).

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図１　GST検出プローブの設計原理の確立：多様な検出シグナル

GSTは癌マーカーとしての診断標的や、抗癌剤開発のための創薬標的として期待されます。これまでに私たちはGSTの反応基質となることで脱保護される保護基（新規分子メカニズム）を考案し、 スウェーデン・カロリンスカ研究所のグループと共同でGSTを細胞内で直接イメージングできる蛍光プローブを開発した図1。さらに、プローブの癌診断法への応用可能性を明らかにしました 。独自の分子メカニズムに基づき様々なプローブ設計が可能になりました。例えばこれまでに、生物発光プローブ、MRIプローブや、抗癌剤のプロドラックを開発しました。これらプローブを用いて、 診断・創薬やケミカルバイオロジーへと大きな研究展開が可能となった。

図2　生体内GSTを検出する化学プローブ

参考文献

1. Aya Shibata, Yukiko Nakano, Mika Ito, Mika Araki, Jie Zhang, Yasuhiko Yoshida, Satoshi Shuto, Bengt Mannervik, Ralf Mogenstern, Yoshihiro Ito, Hiroshi Abe
   Fluorogenic probes using 4-substituted-2-nitrobenzenesulfonyl derivatives as caging groups for the analysis of human glutathione transferase catalyzed reactions
   Analyst accepted (2013).
2. Mika Ito, Aya Shibata, Jie Zhang, Michio Hiroshima, Yasushi Sako, Yukiko Nakano, Kyoko Kojima-Aikawa, Bengt Mannervik, Satoshi Shuto, Yoshihiro Ito, Ralf Morgenstern*, Hiroshi Abe*
   Universal Caging Group for In Cell Detection of Glutathione Transferase Applied to 19F NMR and Bioluminogenic Probes.
   ChemBioChem, 13 (10), 1428-1432, (2012).
3. Jie Zhang, Aya Shibata, Mika Ito, Satoshi Shuto, Yoshihiro Ito, Bengt Mannervik, Hiroshi Abe*, Ralf Morgenstern*
   Synthesis and characterization of a series of highly fluorogenic substrates for glutathione transferases, a general strategy.
   Journal of the American Chemical Society, 133(35), 14109-14119, (2011).
4. Katarina Johansson, Mika Ito, Carolien M. S. Schophuizen, Sherin Mathew T, Vanina D. Heuser, Jie Zhang, Miyuki Shimoji, Marie Vahter, Wee Han Ang, Paul J. Dyson, Aya Shibata, Satoshi Shuto, Yoshihiro, Ito, Hiroshi Abe, Ralf Morgenstern*
   Characterization of New Potential Anticancer Drugs Designed To Overcome Glutathione Transferase Mediated Resistance.
   Molecular Pharmaceutics, 8(5), 1698-1708, (2011).
5. Johan Ålander, Katarina Johansson, Vanina Dahlström Heuser, Henny Farebo, Julia Järvliden, Hiroshi Abe, Aya Shibata, Mika Ito, Yoshihiro Ito, Ralf Morgenstern
   Characterisation of a New Fluorogenic Substrate for Microsomal Glutathione Transferase 1.
   Analytical Biochemistry, 390, 52-56 (2009).
6. Aya Shibata, Kazuhiro Frukawa, Hiroshi Abe*, Satsohi Tsuneda, Yoshihiro Ito
   Rhodamine-based fluorogenic probe for imaging biological thiol.
   Bioorganic Medicinal Chemistry Letters, 18, 2246-2249 (2008).

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図１水にしか溶けない核酸を有機溶媒に溶かす！

核酸分子は、生命現象を担う重要な生体分子であります。一方、人工的な系においても情報記録分子として、或いは有機反応触媒などの機能性分子として利用され始めています。 しかしながら、核酸は水にしか溶解しないため、人工的な系や、有機反応触媒に応用するためには大きな制限がありました。これまでに、我々は核酸の末端をポリエチレングリコールで化学修飾することで、 有機溶媒に完全に可溶化させることに成功しました。有機溶媒可溶化核酸を用いて、有機溶媒中でも核酸の高次構造が水中と同様に保たれることや、有機溶媒中の核酸構造の熱安定性が水中よりも 極めて高いことを見出しました。さらに、酸化反応を触媒するDNAzymeが有機溶媒中でも水中とほぼ同じ効率で触媒作用を示すことを明らかにした。これは有機溶媒中で機能する核酸分子に関する 初めての報告となりました。

図２　有機溶媒中で働く核酸触媒

また、進化分子工学的手法を用いて、核酸アプタマーや核酸触媒を開発することにも成功している。

図３　光ピンセットの開発

参考文献

1. Mingzhe Liu, Seiichi Tada, Mika Ito, Hiroshi Abe, Yoshihiro Ito*
   In vitro selection of a photo-responsive peptide aptamer by ribosome display.
   Chemical Communication, 48, 11871-11873 (2012).
2. Hiroshi Abe*, Naoko Abe, Aya Shibata, Keiji Ito, Yoshiyuki Tanaka, Mika Ito, Hisao Saneyoshi, Satoshi Shuto, Yoshihiro Ito*
   Structure Formation and Catalytic Activity of DNA Dissolved in Organic Solvents.
   Angewandte Chemie International Edition, 51 (26), 6475-6479, (2012).
3. Jeonghwa Kang, Makoto Sakuragi, Aya Shibata, Hiroshi Abe, Takashi Kitajima, Seiichi Tada, Masayoshi Mizutani, Hitoshi Ohmori, Hiroto Ayame, Tae Il Son, Toshiro Aigaki, and Yoshihiro Ito*
   Immobilization of epidermal growth factor on titanium and stainless steel surfaces via dopamine treatment.
   Materials Science and Engineering: C, 32 (8), 2552-2561 (2012).
4. Mingzhe Liu, Muye Xu, Xian Jun Loh, Hiroshi Abe, Takeshi Tsumuraya, Ikuo Fujii, Jun Li, Tae Il Son, Yoshihiro Ito*
   PEGylated antibody in organic media.
   Journal of Bioscience and Bioengineering, 111(5), 564-568 (2011).
5. Mingzhe Liu, Hiroshi Jinmei, Hiroshi Abe, Yoshihiro Ito*
   In vitro selection of a photoresponsive RNA aptamer to hemin.
   Bioorganic & Medicinal Chemistry Letters, 20, 2964–2967 (2010).
6. Mingzhe Liu, Takuma Kagahara, Hiroshi Abe, Yoshihiro Ito*
   In Vitro Selection of Hemin-Binding catalytic RNA.
   Bioorganic Medicinal Chemistry Letters, 19, 1484-1487 (2009).
7. Mingzhe Liu, Takuma Kagahara, Hiroshi Abe, Yoshihiro Ito*
   Direct In Vitro Selection of Hemin-Binding DNA Aptamer with Peroxidase Activity.
   Bulletin of the Chemical Society of Japan, 82, 99-104 (2009).
8. Mingze Liu, Hiroshi Jinmei, Hiroshi Abe*, Yoshihiro Ito*
   Chemical aminoacylation of RNA by an intermolecular adenosine transfer reaction.
   Chemistry Letters, 37, 102-103 (2008).

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図１　ラジカルCグリコシル化反応の開発と医薬品候補化合物の合成

立体選択的なラジカルCグリコシル化反応を開発した。立体電子効果の一つである速度論的なアノマー効果を制御することで、ラジカル反応の立体選択性を制御することができる。 さらに、開発した有機合成反応を用いて細胞内Ca2+放出を調整する重要な細胞内情報伝達物質であるアデノホスチンAの誘導体を種々合成し、 Ca2+放出活性を制御している受容体の構造活性相関を明らかにした。また、様々な有機合成反応のメカニズムを実験・計算化学の両面から明らかにしてきた。

参考文献

1. Mitsuhiro Arisawa*, Yuki Fujii, Hiroshige Kato, Hayato Fukuda, Takashi Matsumoto, Mika Ito, Hiroshi Abe, Yoshihiro Ito, and Satoshi Shuto*
   One-Pot Ring-Closing Metathesis/1,3-Dipolar Cycloaddition through　Assisted Tandem Ruthenium Catalysis: Synthesis of a Dye with Isoindolo[2,1-a]quinoline Structure.
   Angewandte Chemie International Edition, in press (2013).
2. Hiroki Kumamoto*, Sachiko Kawahigashi, Hiromi Wakabayashi, Tomohiko Nakano, Tomoko Miyaike, Yasuyuki Kitagawa, Hiroshi Abe, Mika Ito, Kazuhiro Haraguchi, Jan Balzarini,c Masanori Babad, Hiromichi Tanaka
   Tuning efficiency of the 4-exo-trig cyclization by the electronic effect: ring closure of 3,3-difluoro-4-pentenyl carbon radicals and synthesis of a gem-difluorocyclobutane nucleoside.
   Chemical Communication, 48, 10993-10995 (2012).
3. Mitsuhiro Arisawa*, Yayoi Kasay, Tohru Obata, Takuma Sasaki, Tomonori Nakamura, Takuya Araki, Koujirou yamamoto, Akito Sasaki, Akihito Yamano, Mika Ito, Hiroshi Abe, Yoshihiro Ito, and Satoshi Shuto*
   Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity.
   Journal of Medicinal Chemistry, 55 (18), 8152-8163 (2012).
4. Kazuhiro Haraguchi,* Hisashi Shimada, Keigo Kimura, Genta Akutsu, Hiromichi Tanaka, Hiroshi Abe, Takayuki Hamasaki, Masanori Baba, Elizabeth A. Gullen, Ginger E. Dutschman, Yung-Chi Cheng, and Jan Balzarini
   Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI.
   ACS Medicinal Chemistry Letters, 2(9), 692-697, (2011).
5. Mitsuhiro Arisawa*, Yayoi Kasaya, Tohru Obata, Takuma Sasaki, Mika Ito, Hiroshi Abe, Yoshihiro Ito, Akihito Yamano, Satoshi Shuto*
   Design and Synthesis of Conformationally Restricted Indomethacin Analogues. Identification of Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cyclooxygenase Inhibitory Activity.
   ACS Medicinal Chemistry Letters, 2, 353-357 (2011).
6. Yasuyuki Hirama, Hiroshi Abe, Noriaki Minakawa,* Akira Matsuda
   Synthesis and properties of a novel nucleoside derivative possessing a　2,3,5,6-tetraazabenzo[cd]azulene skeleton.
   Tetrahedron, 66, 8402-8406 (2010).
7. Tetsuya Mochizuki, Akihiko Tanimura, Akihiro Nezu, Mika Ito, Hiroshi Abe, Yoshihiro Ito, Mitsuhiro Arisawa a, Satoshi Shuto*
   Design and synthesis of indole derivatives of adenophostin A. A entry into subtype-selective IP3 receptor ligands.
   Tetrahedron Letters, 51, 977-979 (2010).
8. Takaaki Kobayashi, Mizuki Watanabe, Akira Yoshida, Shizuo Yamada, Mika Ito, Hiroshi Abe, Yoshihiro Ito, Mituhiro Arisawa, Satoshi Shuto*
   Synthesis and structural and pharmacological properties of cyclopropane-based conformationally restricted analogs of 4-methylhistamine as histamine H3/H4 receptor ligands.
   Biorganic Medicinal Chemistry, 18, 1076-1082 (2010).
9. Satoshi Shuto*, Satoshi Ichikawa, Hiroshi Abe, Akira Matsuda.
   Stereoselective glycosylation based on the conformational restriction of pyranoses.
   Yuki Gosei Kagaku Kyokaishi, 66, 50-60 (2008).
10. Hiroki Kumamoto,* Nonoko Takahashi, Tomomoi Shimamura, Hiromichi Tanaka, Kazuo T. Nakamura, Takayuki Hamasaki, Masanori Baba, Hiroshi Abe, MasahikoYano, Nobuyuki Kato.
    Synthesis of (+/-)-9-[c-4, t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (BCA) derivatives branched at the 4'-position based on intramolecular SH2' cyclization.
    Tetrahedron, 64, 1494-1505 (2008).
11. Tetsuya Mochizuki, Yoshihiko Kondo, Hiroshi Abe, Stephen C. Tovey, Skarlatos G. Dedos, Colin W. Taylor, Michael Paul, Barry V. L. Potter, Akira Matsuda, Satoshi Shuto*
    Synthesis of adenophostin A analogues conjugating an aromatic group at the 5'-position as potent IP3 receptor ligands.
    Journal of Medicinal Chemistry, 49, 5750-5758 (2006).
12. Tetsuya Mochizuki, Yoshihiko Kondo, Hiroshi Abe, Collin W. Taylor, Barry V. L. Potter, Akira Matsuda, Satoshi Shuto
    Design and synthesis of 5'-deoxy-5'-phenyladenophostin A, a highly potent IP3 receptor ligand.
    Organic Letters, 8, 1455-1458 (2006).
13. Masaru Terauchi, Hiroshi Abe, Stephen C. Tovey, Skarlatos G. Dedos, Colin W. Taylor, Michael Paul, Melanie Trusselle, Barry V. L. Potter, Akira Matsuda, Satoshi Shuto*
    A systematic study of C-glucoside trisphosphates as myo-inositol trisphosphate receptor ligands. synthesis of alpha -C-glucoside trisphosphates based on the conformational restriction strategy.
    Journal of Medicinal Chemistry, 49, 1900-1909 (2006).
14. Masaru Terauchi, Yumi Yahiro, Hiroshi Abe, Satoshi Ichikawa, Stephen C. Tovey, Skarlatos G. Dedos, Colin W. Taylor, Barry. V. L. Potter, Akira Matsuda, Satoshi Shuto*
    Synthesis of 4,8-anhydro-D-glycero-D-ido-nonanitol 1,6,7-trisphosphate as a novel IP3 receptor ligand using a stereoselective radical cyclization reaction based on a conformational restriction strategy.
    Tetrahedron, 61, 3697-3707 (2005).
15. Yuji Kazuta, Hiroshi Abe, Akira Matsuda, Satoshi Shuto*
    Highly Stereoselective Grignard Addition to Cis-Substituted C-Cyclopropylaldonitrones. The Bisected s-Trans Transition State Can Be Stabilized Effectively by the Lewis Acid-Coordination.
    Journal of Organic Chemistry, 69, 9143-9150 (2004).
16. Masaru Terauchi, Hiroshi Abe, Aakira Matsuda, Satoshi Shuto*
    An efficient synthesis of beta-C-glycosides based on the conformational restriction strategy: Lewis acid promoted silane reduction of the anomeric position with complete stereoselectivity.
    Organic Letters, 6, (21), 3751-3754, (2004).
17. Yuji Kazuta, Hiroshi Abe, Tamotsu Yamamoto, Akira Matsuda, Satoshi Shuto*
    The unusual 1,4-chelation-controlled nucleophilic addition to aldehydes with high stereoselectivity. A systematic study of stereoselectivity in the addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes.
    Tetrahedron, 60, (31), 6689-6703 (2004).
18. Satoshi Shuto*, Masaru Terauchi, YumiYahiro, Hiroshi Abe, Satoshi Ichikawa, Akira Matsuda*
    Stereoselective synthesis of α- and β-C-glucosides via radical cyclization with an allylsilyl tether. Control of the stereoselectivity by changing the conformation of the pyranose ring.
    Tetrahedron Letters.45, 6819 (2004).
19. Kazuya Yamaguchi, Yuji Kazuta, Hiroshi Abe, Akira Matsuda, Satoshi Shuto*
    Construction of a cis-Cyclopropane via Reductive Radical Decarboxylation. Enantioselective Synthesis of cis- and trans-1-Arylpiperazyl-2-phenylcyclopropanes Designed as Antidopaminergic Agents.
    Journal of Organic Chemistry, 68, (24), 9255-9262 (2003).
20. Hiroshi Abe, Masaru Terauchi, Akira Matsuda*, Satoshi Shuto*
    A Study on the Conformation-Anomeric Effect-Stereoselectivity Relationship in Anomeric Radical Reactions, Using Conformationally Restricted Glucose Derivatives as Substrates.
    Journal of Organic Chemistry, 68, (19), 7439-7447 (2003).
21. Yuji Kazuta, Hiroshi Abe, Tamotsu Yamamoto, Akira Matsuda*, Satoshi Shuto*
    A systematic study of the hydride reduction of cyclopropyl ketones with structurally simplified substrates. Highly stereoselective reductions of trans-substituted cyclopropyl ketones via the bisected s-cis conformation.
    Journal of Organic Chemistry, 68, (9), 3511-3521 (2003).
22. Satoru Tamura, Hiroshi Abe, Akira Matsuda*, Satoshi Shuto*
    Control of alpha/beta stereoselectivity in Lewis acid promoted C-glycosidations using a controlling anomeric effect based on the conformational restriction strategy.
    Angewandte Chemie International Edition, 42, (9), 1021-1023 (2003).
23. Satoshi Shuto*, Maki Kanazaki, Isamu Sugimoto, Satoshi Ichikawa, Yuki Nagasawa, Yoshihito Ueno, Hiroshi Abe, Noriaki Minakawa, Makoto Sukeda, Tetsuya Kodama, Makoto Nomura, Akira Matsuda*
    Development of new radical reactions with a vinylsilyl group and their application to the synthesis of branched-chain sugar nucleosides.
    Recent Advances in Nucleosides, 21-55 (2002).
24. Kenji Kuwayama, Seiji Miyauchi, Ryoko Tateoka, Hiroshi Abe, Naoki Kamo*
    Fluorescein uptake by a monocarboxylic acid transporter in human intestinal Caco-2 cells.
    Biochemical Pharmacology, 63, (1), 81-88 (2002).
25. Hiroshi Abe, Satoshi Shuto*, Akira Matsuda*
    Highly alpha- and beta-Selective Radical C-Glycosylation Reactions Using Controlling Anomeric Effect Based on the Conformational Restriction Strategy. A Study on the Conformation-Anomeric Effect- Stereoselectivity Relationship in Anomeric Radical Reactions.
    Journal of the American Chemical Society, 123, (48), 11870-11882 (2001).
26. Hiroshi Abe, Satoshi Shuto*, Satoru Tamura, Akira Matsuda*
    An efficient method for preparing fully O-silylated pyranoses conformationally restricted in the unusual 1C4-form.
    Tetrahedron Letters, 42, 6159-6161 (2001).
27. Satoshi Shuto*, Masaya Fukuoka, Hiroshi Abe, Akira Matsuda*
    Intracellular Ca2+-mobilizing adenine nucleotides. Synthesis and biological activity of cyclic ADP-carbocyclic-ribose and C-glycosidic analog of adenophostin A.
    Nucleosides, Nucleotides & Nucleic Acids, 20, (4-7), 461-470 (2001).
28. Ryoko Tateoka, Hiroshi Abe, Seiji Miyauchi, Satoshi Shuto, Akira Matsuda, Michiya Kobayashi, Katsumi Miyazaki, Naoki Kamo*
    Significance of Substrate Hydrophobicity for Recognition by an Oligopeptide Transporter (PEPT1).
    Bioconjugate Chemistry, 12, (4), 485-492 (2001).
29. Yuji Kazuta, Satoshi Shuto*, Hiroshi Abe, Akira Matsuda*
    The bisected s-trans conformation-controlled highly stereoselective addition of Grignard reagents to C-cyclopropylaldonitrone. An efficient synthesis of 1-phenyl-2-[(S)-1-aminoalkyl]-N,N-diethylcyclopropanecarboxamides, a new class of potent NMDA receptor antagonists.
    Journal of the Chemical Society, Perkin Transactions 1, (6), 599-604 (2001).
    Organic Biomolecular Chemistry, 1, (9), 1634 (2003).
30. Takashi Naka, Noriaki Minakawa, Hiroshi Abe, Daisuke Kaga, Akira Matsuda*
    The Stereoselective Synthesis of 4'-beta-Thioribonucleosides via the Pummerer Reaction.
    Journal of the American Chemical Society, 122, (30), 7233-7243 (2000).
31. Satoshi Shuto*, Masaru Terauchi, Yumi Yahiro, Hiroshi Abe, Satoshi Ichikawa, Akira Matsuda*
    Stereoselective synthesis of alpha- and beta-C-glucosides via radical cyclization with an allylsilyl tether. Control of the stereoselectivity by changing the conformation of the pyranose ring.
    Tetrahedron Letters, 41, (21), 4151-4155 (2000).
32. Hiroshi Abe, Satoshi Shuto*, Akira Matsuda*
    Synthesis of the C-Glycosidic Analogue of Adenophostin A and Its Uracil Congener as Potential IP3 Receptor Ligands. Stereoselective Construction of the C-Glycosidic Structure by a Temporary Silicon-Tethered Radical Coupling Reaction.
    Journal of Organic Chemistry, 65, (14), 4315-4325 (2000).
33. Satoshi Shuto*, Isamu Sugimoto, Hiroshi Abe, Akira Matsuda*
    Mechanistic Study of the Ring-Enlargement Reaction of (3-Oxa-2-silacyclopentyl)methyl Radicals into 4-Oxa-3-silacyclohexyl Radicals. Evidence for a Pentavalent Silicon-Bridging Radical Transition State in 1,2-Rearrangement Reactions of beta-Silyl Radicals.
    Journal of the American Chemical Society, 122, (7), 1343-1351 (2000).
34. Hiroshi Abe, Satoshi Shuto*, Akira Matsuda*
    Nucleosides and nucleotides. 194. Synthesis of the C-glycosidic analog of adenophostin A, a potent IP3 receptor agonist, using a temporary silicon-tethered radical coupling reaction as the key step.
    Tetrahedron Letters, 41, (14), 2391-2394 (2000).
35. Hiroshi Abe, Momoko Satoh, Seiji Miyauchi, Satoshi Shuto, Akira Matsuda, Naoki Kamo*
    Conjugation of Dipeptide to Fluorescent Dyes Enhances Its Affinity for a Dipeptide Transporter (PEPT1) in Human Intestinal Caco-2 Cells.
    Bioconjugate Chemistry, 10, (1), 24-31 (1999).
36. Shun-ichi Hashimoto*, Hiroki Sakamoto, Takeshi Honda, Hiroshi Abe, Sei-ichi Nakamura, Shiro Ikegami*
    Armed-disarmed" glycosidation strategy based on glycosyl donors and acceptors carrying phosphoroamidate as a leaving group: a convergent synthesis of globotriaosylceramide.
    Tetrahedron Letters, 38, (52), 8969-8972 (1997).

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