Controlling protein/cell biofunction by chemical introduction of glycans

• Project/Area Number: 26560438
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Keio University (2016); Institute of Physical and Chemical Research (2014-2015)
• Principal Investigator: Ogura Akihiro 慶應義塾大学, 理工学部(矢上), 助教 (70707843)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 糖鎖 / 糖タンパク質 / ターゲティング / in vivo蛍光イメージング / パターン認識 / 生体内合成 / ネオ糖タンパク質 / 蛍光ラベル化

Outline of Final Research Achievements

We have developed an efficient strategy for synthesis of artificial glycoprotein. This strategy provides the target molecule just by mixing the reagent under mild conditions and does not need prior genetic modification. The glycoproteins thus synthesized were injected to mice and their in vivo kinetics was analyzed. It was revealed that excretion pathway could be controlled and cell selective accumulation was achieved depending on the glycan structure on the protein. Furthermore, first organ-selective metal-catalyzed organic reaction was realized by attaching metal catalyst onto this artificial glycoprotein.

Research Products

• [Int'l Joint Research] カザン大学(ロシア連邦)
• [Int'l Joint Research] カザン大学(ロシア連邦)
• [Journal Article] Sequential double “clicks” toward structurally well-defined heterogeneous N-glycoclusters: The importance of cluster heterogeneity on pattern recognition in vivo (2017)
  • Author(s): L. Latypova, R. Sibgatullina, A. Ogura, K. Fujiki, A. Khabibrakhmanova, T. Tahara, S. Nozaki, S. Urano, K, Tsubokura, H. Onoe, Y. Watanabe, A. Kurbangalieva, K. Tanaka
  • Journal Title: Adv. Sci. Volume: 4 Issue: 2 Pages: 1600394-1600394
  • DOI: 10.1002/advs.201600394
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] In vivo gold complex catalysis within live mice (2017)
  • Author(s): K. Tsubokura, K. K. H. Vong, A. R. Pradipta, A. Ogura, S. Urano, T. Tahara, S. Nozaki, H. Onoe, Y. Nakao, R. Sibgatullina, A. Kurbangalieva, Y. Watanabe, K. Tanaka
  • Journal Title: Angew. Chem. Int. Ed. Volume: 56 Issue: 13 Pages: 3579-3584
  • DOI: 10.1002/anie.201610273
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Total Synthesis and Structural Revision of Clavilactone D (2017)
  • Author(s): Takao, K.; Nemoto, R.; Mori, K.; Namba, A.; Yoshida, K. Ogura, A.
  • Journal Title: Chem. Eur. J. Volume: 23 Issue: 16 Pages: 3828-3831
  • DOI: 10.1002/chem.201700483
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice (2016)
  • Author(s): Tsutsui A, Ogura A, Tahara T, Nozaki S, Urano S, Hara M, Kojima S, Kurbangalieva A, Onoe H, Watanabe Y, Taniguchi N, Tanaka K
  • Journal Title: Organic and Biomolecular Chemistry Volume: - Issue: 24 Pages: 5755-5760
  • DOI: 10.1039/c6ob00098c
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exploring the glycan interaction in vivo: Future prospects of neo-glycoproteins for diagnostics (2016)
  • Author(s): Ogura, A.; Kurbangalieva, A.; Tanaka, K.
  • Journal Title: Glycobiology Volume: 26 Issue: 8 Pages: 804-812
  • DOI: 10.1093/glycob/cww038
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Non-invasive tumor imaging by multivalent glycocluster (2016)
  • Author(s): A. Ogura, T. Tahara, S. Nozaki, H. Onoe, A. Kurbangalieva, Y. Watanabe, K. Tanaka
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 26 Issue: 9 Pages: 2251-2254
  • DOI: 10.1016/j.bmcl.2016.03.046
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin (2016)
  • Author(s): A. Ogura, T. Tahara, S. Nozaki, K. Morimoto, Y. Kizuka, S. Kitazume, M. Hara, S. Kojima, H. Onoe, A. Kurbangalieva, N. Taniguchi, Y. Watanabe, K. Tanaka
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 21797-21797
  • DOI: 10.1038/srep21797
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Azaelectrocyclization on cell surface: convenient and general approach to chemical biology research (2015)
  • Author(s): A. Ogura, K. Tanaka
  • Journal Title: Tetrahedron Volume: 71 Issue: 26-27 Pages: 4518-4521
  • DOI: 10.1016/j.tet.2015.02.063
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Microfluidic Mixing of Polyamine with Acrolein Enables the Detection of the [4+4] Polymerization of Intermediary Unsaturated Imines: The Properties of a Cytotoxic 1,5-Diazacyclooctane Hydrogel (2014)
  • Author(s): Ambara R. Pradipta, Ayumi Tsutsui, Akihiro Ogura, Shinya Hanashima, Yoshiki Yamaguchi, Almira Kurbangalieva, Katsunori Tanaka
  • Journal Title: Synlett Volume: 25 Issue: 17 Pages: 2442-2446
  • DOI: 10.1055/s-0034-1378634
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Metal-catalyzed Organic Reaction in Live Cell (2014)
  • Author(s): 小椋章弘
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 72 Issue: 6 Pages: 726-727
  • DOI: 10.5059/yukigoseikyokaishi.72.726
  • NAID: 130004548620
  • ISSN: 0037-9980, 1883-6526
  • Peer Reviewed
• [Journal Article] Metal-Catalized Organic Reaction in Live Cells: Future Prospect of Time- and Space-Selective Glycan Conjugation In Live Systems (2014)
  • Author(s): A. Ogura, A. Kurbangalieva, K. Tanaka
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 26 Issue: 149 Pages: 73-75
  • DOI: 10.4052/tigg.26.73
  • NAID: 130004841385
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Journal Article] In Vivo Kinetics and Biodistribution Analysis of Neoglycoproteins: Effects of Chemically Introduced Glycans on Proteins (2014)
  • Author(s): A. Ogura, A. Kurbangalieva, K. Tanaka
  • Journal Title: Glycoconj. J Volume: - Issue: 4 Pages: 273-279
  • DOI: 10.1007/s10719-014-9520-3
  • Peer Reviewed
• [Presentation] Synthetic Studies of Callophycoic Acid A (1) (2017)
  • Author(s): Akihiro Sakama、Akihiro Ogura、Ken-ichi Takao
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2017-03-16
• [Presentation] カロフィコ酸Aの全合成研究(2) (2017)
  • Author(s): 住田 渉、坂間 亮浩、小椋 章弘、高尾 賢一
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2017-03-16
• [Presentation] クラビラクトンDの全合成および構造訂正 (2017)
  • Author(s): 森 健斗、小椋 章弘、高尾 賢一
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2017-03-16
• [Presentation] In Vivo Pattern Recognition by Heterogeneous N-glycoclusters: Controlling Excretion and Tumor Targeting (2017)
  • Author(s): Regina Sibgatullina、Liliya Latypova、Katsumasa Fujiki、Akihiro Ogura、Sayaka Urano、Tsuyoshi Tahara、Satoshi Nozaki、Yasuyoshi Watanabe、Almira Kurbangalieva、Katsunori Tanaka
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学（神奈川県・横浜市）
  • Year and Date: 2017-03-16
• [Presentation] カロフィコ酸Aの全合成研究 (2016)
  • Author(s): 坂間 亮浩、吉田 圭佑、小椋 章弘、高尾 賢一
  • Organizer: 第72回有機合成化学協会関東支部（新潟）シンポジウム
  • Place of Presentation: 新潟薬科大学（新潟県・新潟市）
  • Year and Date: 2016-11-26
• [Presentation] 不均一糖鎖クラスターの生体内パターン認識による体内排出、およびがんターゲティングの選択性 (2016)
  • Author(s): Regina Sibgatullina、Liliia Latypova、藤木 勝将、小椋 章弘、田原 強、野崎 聡、浦野 清香、尾上 浩隆、渡辺 恭良、Almira Kurbangalieva、田中 克典
  • Organizer: 第35回日本糖質学会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県・高知市）
  • Year and Date: 2016-09-01
• [Presentation] 蛍光イメージング法によるアルブミンAGEの体内動態 (2016)
  • Author(s): 筒井 歩、小椋 章弘、田原 強、野崎 聡、浦野 清香、尾上 浩隆、渡辺 恭良、谷口 直之、田中 克典
  • Organizer: 第35回日本糖質学会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県・高知市）
  • Year and Date: 2016-09-01
• [Presentation] 不均一な糖鎖クラスターによる腫瘍選択的なターゲティング (2016)
  • Author(s): 小椋章弘、浦野清香、田原強、野崎聡、渡辺恭良、田中克典
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都・京田辺）
  • Year and Date: 2016-03-24
• [Presentation] アルブミンAGEsの生体内動態と集積 (2016)
  • Author(s): 筒井歩、小椋章弘、田原強、野崎聡、浦野静香、渡辺恭良、田中克典
  • Organizer: 日本化学会第96春季年会
  • Place of Presentation: 同志社大学（京都・京田辺）
  • Year and Date: 2016-03-24
• [Presentation] One-pot glycan conjugation to protein via azaelectrocyclization: Dynamics analysis of neoglycoproteins in live animal (2015)
  • Author(s): Akihiro Ogura, Katsunori Tanaka
  • Organizer: Pacifichem 2015
  • Place of Presentation: Honolulu（米国）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] General labeling method of cell surface via azaelectrocyclization (2015)
  • Author(s): Akihiro Ogura, Katsunori Tanaka
  • Organizer: Pacifichem 2015
  • Place of Presentation: Honolulu（米国）
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] 分子イメージングを駆使した天然 N-結合型糖鎖が操る生体内動態の解析 (2015)
  • Author(s): 小椋章弘、田原強、野崎聡、尾上浩隆、渡辺恭良、田中克典
  • Organizer: 第57回天然有機化合物討論会
  • Place of Presentation: 神奈川県民ホール（神奈川・横浜）
  • Year and Date: 2015-09-09
• [Presentation] タンパク質表面へのワンポット複合化による不均一糖鎖クラスターの合成と動物内での動態制御 (2015)
  • Author(s): 小椋章弘、田原強、野崎聡、尾上浩隆、木塚康彦、北爪しのぶ、谷口直之、渡辺恭良、田中克典
  • Organizer: 第34回日本糖質学会年会
  • Place of Presentation: 東京大学（東京・文京）
  • Year and Date: 2015-07-31
• [Presentation] One-pot Fluorescence Labeling of Live Cell Surface and Glycan Conjugation to Protein by RIKEN Click Reaction (2015)
  • Author(s): Akihiro Ogura, Katsunori Tanaka
  • Place of Presentation: Kazan (Volga Region) Federal University（ロシア）
  • Year and Date: 2015-07-03
  • Invited
• [Presentation] Therapeutic in vivo synthetic chemistry: Synthetic studies of bioactive compounds in live mouse (2015)
  • Author(s): Ambara R. Pradipta, Kazuki Tsubokura, Akihiro Ogura, Katsunori Tanaka
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 船橋
  • Year and Date: 2015-03-26 – 2015-03-29
  • Invited
• [Presentation] 6π-アザ電子環状反応による生細胞表面の汎用的なワンポット蛍光ラベル化 (2015)
  • Author(s): 小椋章弘、田中克典
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 船橋
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 糖鎖の化学的ワンポット複合化法と動物個体内での動態解析 (2014)
  • Author(s): 小椋章弘、田原強、野崎聡、森本浩二、木塚康彦、北爪しのぶ、渡辺恭良、谷口直之、田中克典
  • Organizer: 第33回日本糖質学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-08-10 – 2014-08-12
• [Presentation] One-pot Glycan Conjugation to Protein via Azaelectrocyclization: Dynamics Analysis of Neoglycoproteins in Live Animal (2014)
  • Author(s): Akihiro Ogura, Katsunori Tanaka
  • Organizer: 20th International Conference on Organic Synthesis
  • Place of Presentation: Budapest
  • Year and Date: 2014-06-29 – 2014-07-04
• [Presentation] Chemical Introduction of Glycans Precisely Controls the Protein Dynamics and Accumulation in Live Animals (2014)
  • Author(s): Akihiro Ogura, Tsuyoshi Tahara, Satoshi Nozaki, Yasuyoshi Watanabe, Koji Morimoto, Yasuhiko Kizuka, Shinobu Kitazume, Naoyuki Taniguchi, Katsunori Tanaka
  • Organizer: 第3回理研―ソウル大学ワークショップ
  • Place of Presentation: 和光
  • Year and Date: 2014-04-21 – 2014-04-22
• [Remarks] 糖鎖クラスター修飾で分子の生体内挙動を制御する
  • URL: http://www.chem-station.com/blog/2016/04/visualizingtrimming.html
• [Remarks] 糖鎖は不均一であることが重要―糖鎖特有の分子認識機構をマウスで解明―
  • URL: http://www.riken.jp/pr/press/2016/20161128_1/
• [Remarks] Katsunori Tanaka Lab
  • URL: http://www.riken.jp/nori-tanaka-lab/index.html
• [Patent(Industrial Property Rights)] 糖鎖クラスター化アルブミンの開発 (2015)
  • Inventor(s): 田中 克典、渡辺 恭良、小椋 章弘、山本 貴博
  • Industrial Property Rights Holder: 国立研究開発法人理化学研究所、株式会社糖鎖工学研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-06-30
  • Overseas