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Structure-Based Drug Discovery for Prion Disease Using a Novel Binding Simulation
http://hdl.handle.net/10069/37328
http://hdl.handle.net/10069/37328494bf924-4f46-4ec6-b419-dc2591a630e9
名前 / ファイル | ライセンス | アクション |
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EBioMed9_238.pdf (1.9 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-05-19 | |||||
タイトル | ||||||
タイトル | Structure-Based Drug Discovery for Prion Disease Using a Novel Binding Simulation | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Conformational disorders | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Drug discovery | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | In silico screening | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Prion | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Small chemical compounds | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Ishibashi, Daisuke
× Ishibashi, Daisuke× Nakagaki, Takehiro× Ishikawa, Takeshi× Atarashi, Ryuichiro× Watanabe, Ken× Cruz, Felipe A.× Hamada, Tsuyoshi× Nishida, Noriyuki |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The accumulation of abnormal prion protein (PrPSc) converted from the normal cellular isoform of PrP (PrPC) is assumed to induce pathogenesis in prion diseases. Therefore, drug discovery studies for these diseases have focused on the protein conversion process. We used a structure-based drug discovery algorithm (termed Nagasaki University Docking Engine: NUDE) that ran on an intensive supercomputer with a graphic-processing unit to identify several compounds with anti-prion effects. Among the candidates showing a high-binding score, the compounds exhibited direct interaction with recombinant PrP in vitro, and drastically reduced PrPSc and protein-aggresomes in the prion-infected cells. The fragment molecular orbital calculation showed that the van der Waals interaction played a key role in PrPC binding as the intermolecular interaction mode. Furthermore, PrPSc accumulation and microgliosis were significantly reduced in the brains of treated mice, suggesting that the drug candidates provided protection from prion disease, although further in vivo tests are needed to confirm these findings. This NUDE-based structure-based drug discovery for normal protein structures is likely useful for the development of drugs to treat other conformational disorders, such as Alzheimer's disease. | |||||
書誌情報 |
EBioMedicine 巻 9, p. 238-249, 発行日 2016-07 |
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出版者 | ||||||
出版者 | Elsevier B.V. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 23523964 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.ebiom.2016.06.010 | |||||
権利 | ||||||
権利情報 | c 2016 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | EBioMedicine, 9, pp.238-249; 2016 |