<i>Plasmodium falciparum</i> Endoplasmic Reticulum-Resident Calcium Binding Protein Is a Possible Target of Synthetic Antimalarial Endoperoxides, N-89 and N-251
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- Masayuki Morita
- Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan
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- Hitomi Sanai
- Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan
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- Akiko Hiramoto
- Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan
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- Akira Sato
- Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan
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- Osamu Hiraoka
- School of Pharmacy, Shujitsu University, Nishigawara, Okayama 703-8516, Japan
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- Takaya Sakura
- Department of Protozoology, Institute of Tropical Medicine (NEKKEN) and the Global COE Program, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan
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- Osamu Kaneko
- Department of Protozoology, Institute of Tropical Medicine (NEKKEN) and the Global COE Program, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan
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- Araki Masuyama
- Faculty of Engineering, Osaka Institute of Technology, 5-16-1 Ohmiya, Asahiku, Osaka 535-8585, Japan
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- Masatomo Nojima
- Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
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- Yusuke Wataya
- Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan
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- Hye-Sook Kim
- Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan
書誌事項
- 公開日
- 2012-10-25
- 資源種別
- journal article
- DOI
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- 10.1021/pr3005315
- 公開者
- American Chemical Society (ACS)
この論文をさがす
説明
The endoperoxide artemisinin is a current first-line antimalarial and a critical component of the artemisinin-based combination therapies (ACT) recommended by WHO for treatment of Plasmodium falciparum, the deadliest of malaria parasites. However, recent emergence of the artemisinin-resistant P. falciparum urged us to develop new antimalarial drugs. We have shown that synthetic endoperoxides N-89 and its hydroxyl derivative N-251 had high antimalarial activities both in vivo and in vitro. However, the mechanisms including the cellular targets of the endoperoxide antimalarials are not well understood. Thus, in this study, we employed chemical proteomics to survey potential molecular targets of endoperoxides by evaluating P. falciparum proteins capable to associate with endoperoxide structure (N-346, a carboxyamino derivative of N-89). We also analyzed the protein expression profiles of malaria parasites treated with N-89 or N-251 to explore possible changes associated with the drug action. From these experiments, we found that P. falciparum endoplasmic reticulum-resident calcium binding protein (PfERC) had high affinity to the endoperoxide structure (N-346) and was decreased by treatment with N-89 or N-251. PfERC is a member of CREC protein family, a potential disease marker and also a potential target for therapeutic intervention. We propose that the PfERC is a strong candidate of the endoperoxide antimalarial's target.
収録刊行物
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- Journal of Proteome Research
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Journal of Proteome Research 11 (12), 5704-5711, 2012-10-25
American Chemical Society (ACS)
