Therapeutic In Vivo Synthetic Chemistry: Synthesis of Bioactive Polymers In Animals
| Project/Area Number |
18K19154
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
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| Research Institution | Institute of Physical and Chemical Research |
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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) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 生体内合成 / 抗がん活性分子 / 人工金属触媒 / アルブミン / 糖鎖 / 高分子 / 有機合成化学 / 生体内合成化学治療 / 金属触媒反応 |
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| Outline of Final Research Achievements |
The presented work focuses on the development of albumin-based artificial metalloenzymes (ArMs) designed for biological applications. The key foundation of this study is based on the observation that ruthenium metal catalysts bound inside the albumin hydrophobic binding pocket can be resistant to inactivation from biological thiols (i.e. glutathione). For the first bioapplication, investigations were conducted to develop an anticancer prodrug therapy. To elicit cancer-targeting, ArMs were functionalized with N-glycan targeting moieties, which then showed preferential accumulation to varying cancer cells lines (i.e. HeLa, A549, SW620). Subsequent work then showed the successful activation of an umbelliprenin prodrug via ring-closing metathesis. Overall, the work presented in this study highlights the biocompatibility, versatility, and potential applications of albumin-based ArMs.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題で実現した糖鎖付加人工金属触媒は、ルテニウム触媒にかかわらずあらゆる金属触媒反応に展開可能であると考えられる。金属触媒が狙った疾患のところで自在に利用できれば、これまで副作用や安定性の問題で使用できなかった薬理活性分子や創薬候補分子、あるいは診断分子を「現地合成」できる可能性が生まれる。報告者が提唱する「生体内合成化学治療」は、新しい分子を開発するのではなく、既存の分子を有機合成化学の視点で改めて見直す“分子ルネッサンス”であり、創薬や治療を改革すると考えられる。
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Report
(3 results)
Research Products
(127 results)
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[Journal Article] Facile Access to Optically Active 2,6‐Dialkyl‐1,5‐Diazacyclooctanes2019
Author(s)
Chulakova Dilyara R.、Pradipta Ambara R.、Lodochnikova Olga A.、Kuznetsov Danil R.、Bulygina Kseniya S.、Smirnov Ivan S.、Usachev Konstantin S.、Latypova Liliya Z.、Kurbangalieva Almira R.、Tanaka Katsunori
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Journal Title
Chemistry - An Asian Journal
Volume: 14
Issue: 22
Pages: 4048-4054
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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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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[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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