2022 Fiscal Year Final Research Report
Identification of the anti-protozoal compound binding protein for the development and application of novel drug targets.
Project/Area Number |
20K06970
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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Research Institution | Kitasato University |
Principal Investigator |
Ishiyama Aki 北里大学, 感染制御科学府, 特任助教 (70300746)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | pfeIF4A / マラリア原虫 / 結合タンパク質 |
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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Free Research Field |
熱帯病創薬
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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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