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DCフィールド | 値 | 言語 |
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dc.contributor.author | Nagano, Yuki | en |
dc.contributor.author | Arafiles, Jan Vincent V. | en |
dc.contributor.author | Kuwata, Keiko | en |
dc.contributor.author | Kawaguchi, Yoshimasa | en |
dc.contributor.author | Imanishi, Miki | en |
dc.contributor.author | Hirose, Hisaaki | en |
dc.contributor.author | Futaki, Shiroh | en |
dc.contributor.alternative | 長野, 由季 | ja |
dc.contributor.alternative | 今西, 未来 | ja |
dc.contributor.alternative | 川口, 祥正 | ja |
dc.contributor.alternative | 廣瀨, 久昭 | ja |
dc.contributor.alternative | 二木, 史朗 | ja |
dc.date.accessioned | 2022-07-12T07:48:41Z | - |
dc.date.available | 2022-07-12T07:48:41Z | - |
dc.date.issued | 2022-02 | - |
dc.identifier.uri | http://hdl.handle.net/2433/274856 | - |
dc.description.abstract | Stapled peptides are a promising class of conformationally restricted peptides for modulating protein-protein interactions (PPIs). However, the low membrane permeability of these peptides is an obstacle to their therapeutic applications. It is common that only a few hydrophobic amino acid residues are mandatory for stapled peptides to bind to their target proteins. Hoping to create a novel class of membrane-permeable PPI inhibitors, the phenylalanine, tryptophan, and leucine residues that play a critical role in inhibiting the p53-HDM2 interaction were grafted into the framework of CADY2─a cell-penetrating peptide (CPP) having a helical propensity. Two analogues (CADY-3FWL and CADY-10FWL) induced apoptotic cell death but lacked the intended HDM2 interaction. Pull-down experiments followed by proteomic analysis led to the elucidation of nesprin-2 as a candidate binding target. Nesprin-2 is considered to play a role in the nuclear translocation of β-catenin upon activation of the Wnt signaling pathway, which leads to the expression of antiapoptosis proteins and cell survival. Cells treated with the two analogues showed decreased nuclear localization of β-catenin and reduced mRNA expression of related antiapoptotic proteins. These data suggest inhibition of β-catenin nuclear translocation as a possible mode of action of the described cell-penetrating stapled peptides. | en |
dc.language.iso | eng | - |
dc.publisher | American Chemical Society (ACS) | en |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in 'Molecular Pharmaceutics', copyright © 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/acs.molpharmaceut.1c00671. | en |
dc.rights | The full-text file will be made open to the public on 27 December 2022 in accordance with publisher's 'Terms and Conditions for Self-Archiving' | en |
dc.rights | This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 | en |
dc.subject | stapled peptide | en |
dc.subject | cell-penetrating peptide | en |
dc.subject | apoptosis | en |
dc.subject | nesprin-2 | en |
dc.subject | β-catenin | en |
dc.title | Grafting Hydrophobic Amino Acids Critical for Inhibition of Protein–Protein Interactions on a Cell-Penetrating Peptide Scaffold | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Molecular Pharmaceutics | en |
dc.identifier.volume | 19 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 558 | - |
dc.identifier.epage | 567 | - |
dc.relation.doi | 10.1021/acs.molpharmaceut.1c00671 | - |
dc.textversion | author | - |
dc.identifier.pmid | 34958576 | - |
dcterms.accessRights | open access | - |
datacite.date.available | 2022-12-27 | - |
datacite.awardNumber | 18H04403 | - |
datacite.awardNumber | 18H05499 | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PUBLICLY-18H04403/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PLANNED-18H05499/ | - |
dc.identifier.pissn | 1543-8384 | - |
dc.identifier.eissn | 1543-8392 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.awardTitle | 生物機能中分子の細胞導入の分子基盤 | ja |
jpcoar.awardTitle | ケモテクノロジーを利用したユビキチン鎖の機能解析と制御 | ja |
出現コレクション: | 学術雑誌掲載論文等 |
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