Project/Area Number |
20K06970
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
|
Research Institution | Kitasato University |
Principal Investigator |
Ishiyama Aki 北里大学, 感染制御科学府, 特任助教 (70300746)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | pfeIF4A / マラリア原虫 / 結合タンパク質 / 作用標的 / 原虫感染症 / Target protein fishing / リーシュマニア原虫 / トリパノソーマ原虫 / 新規創薬ターゲット |
Outline of Research at the Start |
マラリア、トリパノソーマ症、リーシュマニア症に対し新たな骨格、作用メカニズムを持つ治療薬が必要とされている。本研究ではユニークな骨格を持つ抗原虫活性物質にそれぞれの起因原虫を用いたtarget protein fishingを適用した作用標的タンパク質の同定と創薬展開の加速および新規創薬ターゲットの開拓と創薬スクリーニングへの応用を目指すことで真に効果のある薬剤の創出を目的とする。
|
Outline of Final Research Achievements |
Nilotinib shows inhibitory activity against Plasmodium falciparum, which is absent in tyrosine kinase, therefore, predicted some new mode of action sites that could be a novel target to discover anti-malarial drugs. PfeIF4A, a Nilotinib binding protein of P. falciparum, was first discovered by target protein fishing method using parasite lysate. This protein is essential for parasite survival, and it was reported that DNA and RNA helicase activity by itself. The recombinant pfeIF4A was obtained by the wheat germ protein expression system and assessed in these activities. Unfortunately, the DNA helicase activity was not observed on the partial duplex linear DNA or fork duplex on the M13 single-strand plasmid DNA substrate. The ATPase activity was slightly shown however it was not depending on the DNA substrate. To solve the loss of rpfeIF4A enzymatic activity, it is needed farther studies for involving the difference of protein expression method or substrate characteristics.
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Academic Significance and Societal Importance of the Research Achievements |
PfeIF4Aは過去大腸菌を用いたタンパク発現系で取得され、DNA、RNA helicase阻害活性、ATPase阻害活性が見出された。本研究ではpfeIF4Aを小麦胚芽抽出液を用いた無細胞系で取得し、これら活性の再現が十分ではなかった。その要因についてより詳細に検討することでより正確なpfeIF4Aの特性が解明される。 マラリア治療薬に対する薬剤耐性化が終わりない状況下でpfeIF4A阻害を作用機序にもつ薬剤が見出されることが期待される。
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