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DOI | 10.1038/s41467-019-09044-w |
Design of Peptoid-peptide Macrocycles to Inhibit the beta-catenin TCF Interaction in Prostate Cancer | |
Schneider, Jeffrey A.1; Craven, Timothy W.2,3; Kasper, Amanda C.2; Yun, Chi4; Haugbro, Michael2; Briggs, Erica M.1,5; Svetlov, Vladimir5,6; Nudler, Evgeny5,6; Knaut, Holger4; Bonneau, Richard3; Garabedian, Michael J.1,7; Kirshenbaum, Kent2; Logan, Susan K.1,5 | |
2019-03-19 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | New chemical inhibitors of protein-protein interactions are needed to propel advances in molecular pharmacology. Peptoids are peptidomimetic oligomers with the capability to inhibit protein-protein interactions by mimicking protein secondary structure motifs. Here we report the in silico design of a macrocycle primarily composed of peptoid subunits that targets the beta-catenin:TCF interaction. The beta-catenin:TCF interaction plays a critical role in the Wnt signaling pathway which is over-activated in multiple cancers, including prostate cancer. Using the Rosetta suite of protein design algorithms, we evaluate how different macrocycle structures can bind a pocket on beta-catenin that associates with TCF. The in silico designed macrocycles are screened in vitro using luciferase reporters to identify promising compounds. The most active macrocycle inhibits both Wnt and AR-signaling in prostate cancer cell lines, and markedly diminishes their proliferation. In vivo potential is demonstrated through a zebrafish model, in which Wnt signaling is potently inhibited. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000448044000001 |
WOS关键词 | PROTEIN-PROTEIN INTERACTIONS ; SMALL-MOLECULE INHIBITORS ; ANDROGEN RECEPTOR EXPRESSION ; RELATIVE CELL-PERMEABILITY ; SOLID-PHASE SYNTHESIS ; SIDE-CHAINS ; BETA-CATENIN/TCF4 INTERACTION ; INCREASED SURVIVAL ; SIGNALING PATHWAY ; CYCLIC PEPTOIDS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204265 |
专题 | 资源环境科学 |
作者单位 | 1.NYU, Sch Med, Dept Urol, New York, NY 10016 USA; 2.NYU, Dept Chem, New York, NY 10003 USA; 3.NYU, Ctr Genom & Syst Biol, Dept Biol, New York, NY 10003 USA; 4.NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA; 5.NYU, Sch Med, Biochem & Mol Pharmacol, New York, NY 10016 USA; 6.NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA; 7.NYU, Sch Med, Microbiol, New York, NY 10016 USA |
推荐引用方式 GB/T 7714 | Schneider, Jeffrey A.,Craven, Timothy W.,Kasper, Amanda C.,et al. Design of Peptoid-peptide Macrocycles to Inhibit the beta-catenin TCF Interaction in Prostate Cancer[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Schneider, Jeffrey A..,Craven, Timothy W..,Kasper, Amanda C..,Yun, Chi.,Haugbro, Michael.,...&Logan, Susan K..(2019).Design of Peptoid-peptide Macrocycles to Inhibit the beta-catenin TCF Interaction in Prostate Cancer.NATURE COMMUNICATIONS,9. |
MLA | Schneider, Jeffrey A.,et al."Design of Peptoid-peptide Macrocycles to Inhibit the beta-catenin TCF Interaction in Prostate Cancer".NATURE COMMUNICATIONS 9(2019). |
条目包含的文件 | 条目无相关文件。 |
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