Development of osteoclast differentiation inhibitors based on marine natural products that act on calcium pumps
Project/Area Number |
16H03285
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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 | Keio University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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Keywords | 海洋シアノバクテリア / マクロリド配糖体 / ビセリングビアサイド / 破骨細胞分化抑制 / 人工誘導体 / 構造活性相関 / 抗マラリア活性 / リポペプチド / カルシウムポンプ / 鎖状ペプチド / マクロライド / 破骨細胞分化 / 標的分子探索 / 全合成 / ジャハナイン / 作用機構解析 / HeLa細胞 / 破骨細胞 / 標的分子 / 有機合成 / 生物活性 / クラハイン / 有機化学 |
Outline of Final Research Achievements |
A synthetic method of artificial analogs of biselyngbyaside (BLS), a macrolide glycoside isolated from marine cyanobacteria, has been established. Since glycosylation reactions in the middle or late stage of the synthesis were difficult, sugar moiety was introduced in the early stage. The 18-membered ring construction proceeded in good yields in various cyclization precursors, thus a synthetic method for BLS analogs was established. Natural and synthetic analogs of BLS showed weak antimalarial activities. Affinity purification experiments by using biotin probes of Jahanyne (JHN), a linear lipopeptide isolated from marine cyanobacteria, have identified anti-apoptosis protein (20 kDa) as a candidate of target molecule.
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Academic Significance and Societal Importance of the Research Achievements |
海洋シアノバクテリアから得られたビセリングビアサイド(BLS)は、骨を溶かす破骨細胞の分化を抑制することから新しい骨粗しょう症治療薬のリード化合物として期待される。本研究によりBLS類の種々の人工誘導体を化学合成する方法を確立し、ヒト細胞への毒性を低減した誘導体を合成することができた。さらにBLS類の抗マラリア薬リード化合物としての可能性を見出した。また、リポペプチドであるジャハナインの標的候補タンパク質を見出した。
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Report
(5 results)
Research Products
(73 results)
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[Journal Article] Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium.2017
Author(s)
Iwasaki A, Tadenuma T, Sumimoto S, Ohshiro T, Ozaki K, Kobayashi K, Teruya T, Tomoda H, Suenaga K.
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Journal Title
J Nat Prod.
Volume: 80
Issue: 4
Pages: 1161-1166
DOI
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Peer Reviewed
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[Journal Article] Janadolide, a Cyclic Polyketide-Peptide Hybrid Possessing a t-butyl Group from an Okeania sp. Marine Cyanobacterium.2016
Author(s)
Hidetoshi Ogawa, Arihiro Iwasaki, Shinpei Sumimoto, Yuki Kanamori, Osamu Ohno, Masato Iwaztsuki, Aki Ishiyama, Rei Hokari, Kazuhiko Otoguro, Satoshi Omura, and Kiyotake Suenaga
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Journal Title
Journal of Natural Products
Volume: 79
Issue: 7
Pages: 1862-1866
DOI
Related Report
Peer Reviewed
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[Presentation] Total Synthesis and Biological Evaluations of Biselyngbyasides2018
Author(s)
SATO, Eisuke; SATO, Miho; TABANE, Yurika; NAKAJIMA, Naoya; OHKUBO, Akifumi; IWATSUKI, Masato; OGAWA, Haruo; TOYOSHIMA, Chikashi; MORITA, Maho; IWASAKI, Arihiro; SUENAGA, Kiyotake
Organizer
日本化学会第98春季年会(日本大学船橋キャンパス)
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