Item type |
学術雑誌論文 / Journal Article(1) |
公開日 |
2022-05-12 |
タイトル |
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タイトル |
Cyclic Peptide-Based Biologics Regulating HGF-MET |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
ID登録 |
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ID登録 |
10.24517/00066040 |
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ID登録タイプ |
JaLC |
著者 |
Sato, Hiroki
Imamura, Ryu
Suga, Hiroaki
Matsumoto, Kunio
Sakai, Katsuya
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著者別表示 |
佐藤, 拓輝
今村, 龍
松本, 邦夫
酒井, 克也
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提供者所属 |
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内容記述タイプ |
Other |
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内容記述 |
金沢大学がん進展制御研究所 |
書誌情報 |
International Journal of Molecular Sciences
巻 21,
号 21,
p. 7977,
発行日 2020-10-27
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ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1422-0067 |
ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1661-6596 |
NCID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA12038549 |
DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.3390/ijms21217977 |
出版者 |
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出版者 |
MDPI |
抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Using a random non-standard peptide integrated discovery system, we obtained cyclic peptides that bind to hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor. (MET) HGF-inhibitory peptide-8 (HiP-8) selectively bound to two-chain active HGF, but not to single-chain precursor HGF. HGF showed a dynamic change in its molecular shape in atomic force microscopy, but HiP-8 inhibited dynamic change in the molecular shape into a static status. The inhibition of the molecular dynamics of HGF by HiP-8 was associated with the loss of the ability to bind MET. HiP-8 could selectively detect active HGF in cancer tissues, and active HGF probed by HiP-8 showed co-localization with activated MET. Using HiP-8, cancer tissues with active HGF could be detected by positron emission tomography. HiP-8 seems to be applicable for the diagnosis and treatment of cancers. In contrast, based on the receptor dimerization as an essential process for activation, the cross-linking of the cyclic peptides that bind to the extracellular region of MET successfully generated an artificial ligand to MET. The synthetic MET agonists activated MET and exhibited biological activities which were indistinguishable from the effects of HGF. MET agonists composed of cyclic peptides can be manufactured by chemical synthesis but not recombinant protein expression, and thus are expected to be new biologics that are applicable to therapeutics and regenerative medicine. |
権利 |
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権利情報 |
Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
関連URI |
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識別子タイプ |
URI |
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関連識別子 |
https://www.mdpi.com/1422-0067/21/21/7977/htm |
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関連名称 |
https://www.mdpi.com/1422-0067/21/21/7977/htm |
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識別子タイプ |
URI |
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関連識別子 |
https://www.mdpi.com/journal/ijms |
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関連名称 |
https://www.mdpi.com/journal/ijms |
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識別子タイプ |
URI |
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関連識別子 |
https://v2.sherpa.ac.uk/id/publisher/487 |
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関連名称 |
https://v2.sherpa.ac.uk/id/publisher/487 |