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2019 Fiscal Year Final Research Report

Identification of the anti-protozoal compound binding protein for the development of novel drug targets.

Research Project

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Project/Area Number 17K01951
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomolecular chemistry
Research InstitutionKitasato University

Principal Investigator

Ishiyama Aki  北里大学, 感染制御科学府, 特任助教 (70300746)

Project Period (FY) 2017-04-01 – 2020-03-31
Keywordstarget 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
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.

Free Research Field

寄生虫学

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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Published: 2021-02-19  

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