Development of Lamellarin Type Anti-HIV Compoundswith a New Mechanism of Action
| Project/Area Number |
22510235
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Nagasaki University |
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Principal Investigator |
FUKUDA Tsutomu 長崎大学, 大学院・工学研究科, 助教 (80295097)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Yoshinao 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (30273527)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ラメラリンサルフェート / 抗HIV剤 / 構造活性相関 / 侵入阻害 / 抗ＨＩＶ剤 / 坑HIV剤 |
|---|
| Research Abstract |
Marine natural product lamellarin α 20-sulfate has been known to inhibit integrase with an IC50 of 22 μM and growth of the HIV-1 virus in cell culture with an IC50 of 8 μM. The MTT assay of lamellarin α 20-sulfate toward HeLa cells displayed the least toxicity of 274 μM. Despite the promising feature of lamellarin α 20-sulfate as a new lead anti-HIV-1 agent, the structure-activity relationships of lamellarin sulfates have scarcely been investigated. In this research, we have prepared sulfated lamellarin analogues using a synthetic strategy developed in our laboratories. The structure-activity relationship study revealed that the pentacyclic lamellarin core and the sulfate group are essential for anti-HIV-1 activity. Confocal laser microscopic analyses and cell-cell fusion experiments suggested that the anti-HIV-1 activity of lamellarin sulfates are caused by inhibition of the virus entry step rather than the previously indicated integration step.
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Report
(4 results)
Research Products
(53 results)
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[Presentation] ラメラリンの軸不斉を利用したプロテインキナーゼ阻害選択性の制御2012
Author(s)
吉田賢佑, 糸山諒介, 山平昌志, 田中淳二, Nadege Loaec, Olivier Lozach, Emilie Durieu, Laurent Meijer, 福田 勉, 石橋郁人, 岩尾正倫
Organizer
第30回メディシナルケミストリーシンポジウム
Place of Presentation
東京
Related Report
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[Presentation] ラメラリンの軸不斉を利用したプロテインキナーゼ阻害選択性の制御2012
Author(s)
吉田賢佑, 糸山諒介, 山平昌志, 田中淳二, Nadege Loaec, Olivier Lozach, Emilie Durieu, Laurent Meijer, 福田勉, 石橋郁人, 岩尾正倫
Organizer
第30回メディシナルケミストリーシンポジウム
Place of Presentation
タワーホール船堀（東京都）
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