A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein-Protein Interactions by Epitope and Arginine Grafting
DC Field | Value | Language |
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dc.contributor.author | Fujiwara, Daisuke | - |
dc.contributor.author | Kitada, Hidekazu | - |
dc.contributor.author | Oguri, Masahiro | - |
dc.contributor.author | Nishihara, Toshio | - |
dc.contributor.author | Michigami, Masataka | - |
dc.contributor.author | Shiraishi, Kazunori | - |
dc.contributor.author | Yuba, Eiji | - |
dc.contributor.author | Nakase, Ikuhiko | - |
dc.contributor.author | Im, Haeri | - |
dc.contributor.author | Cho, Sunhee | - |
dc.contributor.author | Joung, Jong Young | - |
dc.contributor.author | Kodama, Seiji | - |
dc.contributor.author | Kono, Kenji | - |
dc.contributor.author | Ham, Sihyun | - |
dc.contributor.author | Fujii, Ikuo | - |
dc.date.available | 2021-02-22T11:25:04Z | - |
dc.date.issued | 2016-08 | - |
dc.identifier.issn | 1433-7851 | - |
dc.identifier.issn | 1521-3773 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9501 | - |
dc.description.abstract | The design of inhibitors of intracellular protein-protein interactions (PPIs) remains a challenge in chemical biology and drug discovery. We propose a cyclized helix-loop-helix (cHLH) peptide as a scaffold for generating cell-permeable PPI inhibitors through bifunctional grafting: epitope grafting to provide binding activity, and arginine grafting to endow cell-permeability. To inhibit p53-HDM2 interactions, the p53 epitope was grafted onto the C-terminal helix and six Arg residues were grafted onto another helix. The designed peptide cHLHp53-R showed high inhibitory activity for this interaction, and computational analysis suggested a binding mode for HDM2. Confocal microscopy of cells treated with fluorescently labeled cHLHp53-R revealed cell membrane penetration and cytosolic localization. The peptide inhibited the growth of HCT116 and LnCap cancer cells. This strategy of bifunctional grafting onto a well-structured peptide scaffold could facilitate the generation of inhibitors for intracellular PPIs. | - |
dc.format.extent | 4 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | WILEY-V C H VERLAG GMBH | - |
dc.title | A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein-Protein Interactions by Epitope and Arginine Grafting | - |
dc.type | Article | - |
dc.publisher.location | 독일 | - |
dc.identifier.doi | 10.1002/anie.201603230 | - |
dc.identifier.scopusid | 2-s2.0-84979737381 | - |
dc.identifier.wosid | 000383473600012 | - |
dc.identifier.bibliographicCitation | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v.55, no.36, pp 10612 - 10615 | - |
dc.citation.title | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | - |
dc.citation.volume | 55 | - |
dc.citation.number | 36 | - |
dc.citation.startPage | 10612 | - |
dc.citation.endPage | 10615 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR PATHWAY | - |
dc.subject.keywordPlus | IN-VIVO ACTIVATION | - |
dc.subject.keywordPlus | P53-MDM2 INTERACTION | - |
dc.subject.keywordPlus | CANCER-THERAPY | - |
dc.subject.keywordPlus | P53 | - |
dc.subject.keywordPlus | MDM2 | - |
dc.subject.keywordPlus | ANTAGONISTS | - |
dc.subject.keywordPlus | SELECTION | - |
dc.subject.keywordPlus | LIBRARY | - |
dc.subject.keywordPlus | DOMAIN | - |
dc.subject.keywordAuthor | cell-penetrating peptides | - |
dc.subject.keywordAuthor | epitope grafting | - |
dc.subject.keywordAuthor | helix-loop-helix peptides | - |
dc.subject.keywordAuthor | inhibitors | - |
dc.subject.keywordAuthor | protein-protein interactions | - |
dc.identifier.url | https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201603230 | - |
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