| アイテムタイプ |
itemtype_ver1(1) |
| 公開日 |
2025-01-24 |
| タイトル |
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|
タイトル |
Inhibition of Lysosomal Cathepsin A and Neuraminidase 1 Interaction by Anti-Obesity Cyclic Peptide |
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言語 |
en |
| 著者 |
Sun, Yiting
Dakiiwa, Ayumi
Zhang, Menghua
Shibata, Takahiro
Kita, Masaki
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| アクセス権 |
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|
アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利 |
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|
権利情報 |
"This is the peer reviewed version of the following article: [Y. Sun, A. Dakiiwa, M. Zhang, T. Shibata, M. Kita, Chem. Eur. J. 2024, 30, e202402049. https://doi.org/10.1002/chem.202402049], which has been published in final form at [https://doi.org/10.1002/chem.202402049]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited." |
|
言語 |
en |
| 内容記述 |
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内容記述タイプ |
Abstract |
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内容記述 |
Chronic inflammation in adipose tissue is associated with metabolic disorders such as obesity and type 2 diabetes. Novel small molecules targeting adipocyte differentiation and fat accumulation offer potential for new anti-inflammatory and anti-obesity drugs. Here we show that the marine cyclic heptapeptide stylissatin A and its analogs (SAs) inhibit membranous neuraminidase 1 (Neu1) function by interacting with lysosomal protective protein cathepsin A (PPCA). Neu1 has been less explored as a therapeutic target due to the genetic defects leading to neurodegenerative disorders. However, unlike traditional neuraminidase inhibitors, SAs don't directly bind to Neu1 but modulate the molecular chaperone activity of PPCA. SAs caused degradation of perilipin 1 around lipid droplets and inhibited fat accumulation, along with decrease in membranous Neu1. Molecular docking and molecular dynamics simulations revealed that SAs interacted with activated PPCA at the Neu1 binding site. Focusing on this newfound protein–protein interaction inhibition mechanism could lead to the development of pharmaceuticals with fewer side effects. |
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言語 |
en |
| 出版者 |
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出版者 |
Wiley |
|
言語 |
en |
| 言語 |
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|
言語 |
eng |
| 資源タイプ |
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資源タイプresource |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連情報 |
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|
関連タイプ |
isVersionOf |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1002/chem.202402049 |
| 収録物識別子 |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
0947-6539 |
| 書誌情報 |
en : Chemistry-a European Journal
巻 30,
号 56,
p. e202402049,
発行日 2024-10-08
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| ファイル公開日 |
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|
日付 |
2025-10-08 |
|
日付タイプ |
Available |
SA probe 2023_CEJ_MS_r1_f.pdf (2.4 MB)
