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https://hdl.handle.net/20.500.14094/0100479012
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2024-04-23
17:17 集計
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0100479012 (fulltext)
pdf
1.89 MB
14
Supporting Information (dataset)
pdf
1.41 MB
9
メタデータ
ファイル出力
メタデータID
0100479012
アクセス権
open access
出版タイプ
Accepted Manuscript
タイトル
Micelle-like Nanoassemblies of Short Peptides Create Antimicrobial Selectivity in a Conventional Antifungal Drug
著者
Morita, Kenta ; Nishimura, Yuya ; Ishii, Jun ; Maruyama, Tatsuo
著者ID
A2788
研究者ID
1000060804127
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=4c6fa0d9aef47a7b520e17560c007669
著者名
Morita, Kenta
森田, 健太
モリタ, ケンタ
所属機関名
工学研究科
著者ID
A1345
研究者ID
1000040728218
著者名
Nishimura, Yuya
西村, 勇哉
ニシムラ, ユウヤ
所属機関名
科学技術イノベーション研究科
著者ID
A1290
研究者ID
1000040512546
ORCID
0000-0003-2568-515X
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=c06bf6c66d97f49e520e17560c007669
著者名
Ishii, Jun
石井, 純
イシイ, ジュン
所属機関名
先端バイオ工学研究センター
著者ID
A1709
研究者ID
1000030346811
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=9932913cd2f5b830520e17560c007669
著者名
Maruyama, Tatsuo
丸山, 達生
マルヤマ, タツオ
所属機関名
工学研究科
収録物名
ACS Applied Nano Materials
巻(号)
6(2)
ページ
1432-1440
出版者
American Chemical Society
刊行日
2023-01-27
公開日
2023-12-23
抄録
The discovery of novel antibacterial drugs against infectious diseases has decreased over the past few decades because of their poor cost performance. In this study, we report that the nanoassembly of a short-peptide hydrogelator (P1) endowed novel antifungal selectivity to a conventional antifungal drug, amphotericin B (AmB), which expands its application spectrum. Clinical use of AmB is limited because of poor water solubility and poor selectivity in its toxicity, which often causes harmful effects on tissues. P1 was the low-molecular-weight hydrogelator (LMWHg) that showed low cytotoxicity and was enzymatically degraded. In general, an LMWHg entraps foreign hydrophobic molecules inside the hydrophobic space in the self-assembled body. P1 successfully solubilized AmB in water as a form of a nanocomplex (NC) that had a chain-like structure. The NCs showed remarkably low toxicity toward Saccharomyces cerevisiae as a model fungus when compared with free AmB, meaning that P1 suppressed the antifungal activity of AmB via coassembly. The suppressed antifungal activity of AmB recovered when P1 in the NCs was degraded by a protease to liberate AmB from the coassembly with P1. P1 at a high concentration formed a hydrogel incorporating AmB (AmB-P1 gel), in which the antifungal activity of AmB was suppressed as well as that in the NC. The coassembly with AmB affected the morphology of the P1 self-assembly. While S. cerevisiae that did not secrete proteases formed a colony on the AmB-P1 gel, Aspergillus oryzae that secreted proteases did not grow on the AmB-P1 gel at all, resulting in the selective killing of the fungus. Because some of malignant, infectious fungi secrete proteases, the coassembly strategy of conventional antifungal drugs with self-assembling molecules should lead to “drug repositioning” of approved drugs in the health and medical fields.
キーワード
antifungal drug
drug repositioning
low-molecular-weight gelator
peptide
self-assembly
カテゴリ
科学技術イノベーション研究科
工学研究科
先端バイオ工学研究センター
学術雑誌論文
権利
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Nano Materials, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/articlesonrequest/AOR-SCUDNVTDFEEIMVCDFTMD
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資源タイプ
journal article
言語
English (英語)
eISSN
2574-0970
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関連情報
DOI
https://doi.org/10.1021/acsanm.2c05183
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