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Synthesis and Biological Evaluation of Novel 2-(Benzofuran-2-yl)-chromone Derivatives for In Vivo Imaging of Prion Deposits in the Brain
http://hdl.handle.net/10069/00041782
http://hdl.handle.net/10069/00041782db4c8db1-9535-4f5e-b308-548f19250991
名前 / ファイル | ライセンス | アクション |
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ACSID8_1869.pdf (1.3 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-10-13 | |||||
タイトル | ||||||
タイトル | Synthesis and Biological Evaluation of Novel 2-(Benzofuran-2-yl)-chromone Derivatives for In Vivo Imaging of Prion Deposits in the Brain | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Prion disease | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PrPSc | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | amyloid | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 2-(benzofuran-2-yl)-chromone | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | single photon emission computed tomography (SPECT) | |||||
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 |
Nakaie, Mari
× Nakaie, Mari× Katayama, Fumihiro× Nakagaki, Takehiro× Yoshida, Sakura× Kawasaki, Masao× Nishi, Kodai× Ogawa, Kazuma× Toriba, Akira× Nishida, Noriyuki× Nakayama, Morio× Fuchigami, Takeshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Prion diseases are fatal neurodegenerative disorders caused by deposition of scrapie prion protein aggregates (PrPSc) in the brain. We previously reported that styrylchromone (SC) and benzofuran (BF) derivatives have potential as imaging probes for PrPSc. To further improve their properties, we designed and synthesized 2-(benzofuran-2-yl)-chromone (BFC) derivatives hybridized with SC and BF backbones as novel single-photon emission computed tomography probes for the detection of cerebral PrPSc deposits. Recombinant mouse prion protein (rMoPrP) aggregates and mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice were used to evaluate the binding properties of BFC derivatives to PrPSc. The BFC derivatives exhibited high binding affinities (equilibrium dissociation constant [Kd] = 22.6–47.7 nM) for rMoPrP aggregates. All BFC derivatives showed remarkable selectivity against amyloid beta aggregates. Fluorescence microscopy confirmed that the fluorescence signals of the BFC derivatives corresponded to the antibody-positive deposits of PrPSc in mBSE-infected mouse brains. Among the BFC derivatives, [125I]BFC-OMe and [125I]BFC-NH2 exhibited high brain uptake and favorable washout from the mouse brain. In vitro autoradiography demonstrated that the distribution of [125I]BFC-OMe in the brain tissues of mBSE-infected mice was co-localized with PrPSc deposits. Taken together, BFC derivatives appear to be promising prion imaging probes. | |||||
書誌情報 |
ACS Infectious Diseases 巻 8, 号 9, p. 1869-1882, 発行日 2022-09-09 |
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出版者 | ||||||
出版者 | American Chemical Society | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2373-8227 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1021/acsinfecdis.2c00142 | |||||
権利 | ||||||
権利情報 | This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Infectious Diseases, copyright (c) American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsinfecdis.2c00142 | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | ACS Infectious Diseases, 8(9), pp. 1869-1882; 2022 |