Identification of the anti-protozoal compound binding protein for the development of novel drug targets.
| Project/Area Number |
17K01951
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Kitasato University |
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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) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | target protein fishing / マラリア原虫 / リーシュマニア原虫 / トリパノソーマ原虫 / 抗原虫活性物質 / ケミカルバイオロジー / Target protein fishing / 原虫感染症 / 天然物化学 |
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| Outline of Final Research Achievements |
We reported tyrosine kinase inhibitor nilotinib showed antimalarial activity both in vitro and in vivo. However, it is clear that Pasmodium dose not have tyrosine kinase, indicate presence of novel mode of action (MOA). To identify the antimalarial MOA of nilotinib, target protein fishing was used for obtaining binding proteins. Five binding proteins were obtained and a part of them were identified endplasmin homolog, RNA helicase (pfeIF4A) and a membrane protein A. PfeIF4A is an indispensable factor for malaria parasite (from PlasmoDB) and it might be lead to development for new target.
Protein expression of pfeIF4A and creating of nilotinib resistant P.falciparum are ongoing to validate the MOA.
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| Academic Significance and Societal Importance of the Research Achievements |
Nilotinibの結合タンパク質の１つとして得られたpfeIF4Aは原虫にとって必須因子であり、新たな創薬ターゲットが見出されたと言える。機能未知な膜タンパク質Aは創薬標的分子として応用が可能か、あるいはマラリア原虫の生物学的研究および診断薬などへの応用が可能であるかを検証することに意義がある。現在使用されている抗原虫剤の多くは作用標的が未解明なものが多く今後の進展が期待される。本研究で得られた結果は輸入感染症対策、新興再興感染症対策に繋がり、また人類の健康に貢献するものである。
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Report
(4 results)
Research Products
(1 results)
