Therapeutic In Vivo Synthetic Chemistry by Transition Metal Catalyzed Amidation
Project/Area Number |
16H03287
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomolecular chemistry
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Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Tanaka Katsunori 国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (00403098)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
|
Keywords | 化学合成 / 生体分子 / 蛋白質 / 糖鎖 / 生体内合成化学治療 |
Outline of Final Research Achievements |
If we could synthesize these drug candidates at the disease tissue directly in vivo, potential benefits are that side effects to other organs may be lessened and the therapeutic window of drug activity can be prolonged before decomposition. We referred to this new clinical approach as "Therapeutic In Vivo Synthetic Chemistry". One promising strategy is to use transition metal catalyzed reaction in vivo. We developed new metal-catalyzed (or mediated) transformations in biologically relevant media. To perform this reaction selectively in vivo at targeted organs, we designed a strategy that conjugates transition metal catalysts to glycoclusters, which quickly and selectively accumulate to target organs. Following injection of these metal conjugated glycoclusters into mice, we then injected the reagents to label or synthesizing the molecules at the targeted organs in mice. Our strategy led to the first example of organ selective metal catalyzed reactions.
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Academic Significance and Societal Importance of the Research Achievements |
報告者らが開発した方法を用いて狙った臓器で選択的に金属触媒反応を起こせば、がんなどの疾患部位で、直接、薬などの生理活性分子を合成できると期待できる。さまざまな金属触媒反応に展開できると考えられ、体内で薬の合成が可能となる。その結果、薬が疾患部位以外で作用して起きる副作用の問題、あるいはペプチドなど不安定な薬の体内での安定性の問題を解決できると期待できる。過去、ドロップアウトしてきた薬理活性分子を生体内で直接見直す新戦略であり、創薬化学やプロドラッグ、あるいはドラッグデリバリーシステムにおける「分子機能のルネッサンス」となる。
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Report
(4 results)
Research Products
(211 results)
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[Journal Article] Branched Sialylated <i>N</i>-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H2018
Author(s)
M. Handa-Narumi, T. Yoshimura, H. Konishi, Y. Fukata, Y. Manabe, K. Tanaka, G.-m. Bao, H. Kiyama, K. Fukase, K. Ikenaka
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Journal Title
Cell Structure and Function
Volume: 43
Issue: 2
Pages: 141-152
DOI
NAID
ISSN
0386-7196, 1347-3700
Related Report
Peer Reviewed / Open Access
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[Journal Article] Viable strategy for screening the effects of glycan heterogeneity on target organ adhesion and biodistribution in live mice2018
Author(s)
A. Ogura, S. Urano, T. Tahara, S. Nozaki, R. Sibgatullina, K. Vong, T. Suzuki, N. Dohmae, A. Kurbangalieva, Y. Watanabe, K. Tanaka
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Journal Title
Chem. Commun.
Volume: 54
Issue: 63
Pages: 8693-8696
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Reactivity of anti-HNK-1 antibodies to branched O-mannose glycans associated with demyelination2017
Author(s)
K. Sakuda, Y. Kizuka, Y. Yamaguchi, K. Tanaka, K. Ogiwara, T. Segawa, Y. Hagiwara, I. Matsuo, H. Ogawa, N. Taniguchi, S. Kitazume
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 487
Issue: 2
Pages: 450-456
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vivo gold complex catalysis within live mice2017
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
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Journal Title
Angew. Chem. Int. Ed.
Volume: 56
Issue: 13
Pages: 3579-3584
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Sequential double “clicks” toward structurally well-defined heterogeneous N-glycoclusters: The importance of cluster heterogeneity on pattern recognition in vivo2017
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
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Journal Title
Adv. Sci.
Volume: 4
Issue: 2
Pages: 1600394-1600394
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation.2016
Author(s)
Iwata, T., Otsuka, S., Tsubokura, K., Kurbangalieva, A., Arai, D., Fukase, K., Nakao, Y., Tanaka, K.
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Journal Title
Chem. Eur. J.
Volume: 22
Issue: 41
Pages: 14707-14716
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 1,5-Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid-β(1-40) 10. 1,5-Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid-β(1-40) Fibrillization2016
Author(s)
A. Tsutsui, T. Zako, T. Bu, Y. Yamaguchi, M. Maeda, K. Tanaka
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Journal Title
Adv. Sci.
Volume: 3
Issue: 10
Pages: 1600082-1600082
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice2016
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
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Journal Title
Organic and Biomolecular Chemistry
Volume: -
Issue: 24
Pages: 5755-5760
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] In vivo gold catalyzed reaaction using glycocluster as organ selective metal carrier2018
Author(s)
Kazuki Tsubokura, Kenward Vong, Sayaka Urano, Lin Yixuan, Tsuyoshi Tahara, Satoshi Nozaki, Regina Sibgatullina, Almira Kurbangalieva, Yasuyoshi Watanabe, Yoichi Nakao, Katsunori, Tanaka
Organizer
東京糖鎖研究会(GlycoTOKYO2018)、理化学研究所(埼玉県和光市)
Related Report
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[Presentation] In vivo gold catalyzed reaction using glycocluster as organ selective metal carrier2018
Author(s)
Kazuki Tsubokura, Kenward Vong, Sayaka Urano, Lin Yixuan, Tsuyoshi Tahara, Satoshi Nozaki, Regina Sibgatullina, Almira Kurbangalieva, Yasuyoshi Watanabe, Yoichi Nakao, Katsunori Tanaka
Organizer
29th International Carbohydrate Symposium, Universidade de Lisboa(Lisbon, Portugal)
Related Report
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[Presentation] Therapeutic in vivo synthetic chemistry2017
Author(s)
Katsunori Tanaka
Organizer
International Symposium, “Systems Glycobiology and Beyond” -Toward a bridge between fundamental research and applied science-, RIKEN Wako campus, Suzuki Umetaro Hall(Wako, Saitama)
Related Report
Int'l Joint Research / Invited
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[Presentation] Organic Synthesis in Live Animals: Therap2017
Author(s)
Katsunori Tanaka
Organizer
RIKEN-Max Planck Joint Research Center for Systems Chemical Biology - The Sixth Symposium
Place of Presentation
RIKEN Wako campus, Suzuki Umetaro Hall(Wako, Saitama)
Related Report
Int'l Joint Research / Invited
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[Presentation] Therapeutic In Vivo Synthetic Chemistry2017
Author(s)
Katsunori Tanaka
Organizer
The 3rd RIKEN-Academia Sinica Joint Conference: Focus on Chemistry and Chemical Biology
Place of Presentation
RIKEN Wako campus, Suzuki Umetaro Hall(Wako, Saitama)
Related Report
Int'l Joint Research / Invited
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[Presentation] 見過ごされていたアルキルアジドの反応性に基づくアクロレインの検出2016
Author(s)
Ambara R. Pradipta, Misako Taichi, Ikuhiko Nakase, Shinobu Kitazume, Naoyuki Taniguchi, Katsunori Tanaka
Organizer
分子システム研究第5回春季研究会
Place of Presentation
かんぽの宿熱海(神奈川県熱海市)
Year and Date
2016-05-13
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[Presentation] Polyamide and AGEs2016
Author(s)
Ayumi Tsutsui, Katsunori Tanaka
Organizer
3rd RIKEN - KFU Workshop
Place of Presentation
Kazan Federal University(Kazan, Russia)
Related Report
Int'l Joint Research
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[Presentation] Cycloadditions of imines2016
Author(s)
Ambara R. Pradipta, Katsunori Tanaka
Organizer
3rd RIKEN - KFU Workshop
Place of Presentation
Kazan Federal University(Kazan, Russia)
Related Report
Int'l Joint Research
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