• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一种环化螺旋-环-螺旋肽作为雌激素受体α与共激活因子SRC1相互作用的细胞膜可渗透抑制剂的分子支架。

A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for Cell-Membrane Permeable Inhibitors for the Interaction Between Estrogen Receptor α and Coactivator SRC1.

作者信息

Fujiwara Daisuke, Inaura Shunsuke, Tanaka Yuna, Ito-Harashima Sayoko, Yamaguchi-Nomoto Asako, Kawanishi Masanobu, Yagi Takashi, Nakase Ikuhiko, Fujii Ikuo

机构信息

Graduate School of Science, Osaka Metropolitan University, Gakuen-cho 1-1, Sakai, Osaka, 599-8531, Japan.

Graduate School of Science, Osaka Prefecture University, Gakuen-cho 1-1, Sakai, Osaka, 599-8531, Japan.

出版信息

Chembiochem. 2025 Jul 11;26(13):e202500232. doi: 10.1002/cbic.202500232. Epub 2025 Jun 20.

DOI:10.1002/cbic.202500232
PMID:40407028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12247020/
Abstract

The molecular design of inhibitors against intracellular protein-protein interactions (PPIs) is of interest for drug discovery and chemical biology. Herein, a novel cyclized helix-loop-helix (cHLH) peptide that inhibited the intracellular PPI between estrogen receptor alpha (ERα) and coactivator SRC1 are designed. The peptide, cHLH-ERα, bound to ERα and inhibited the interaction between ERα and the coactivator SRC1. Cellular imaging and yeast reporter assays showed that cHLH-ERα penetrated the cell membrane and exhibited antagonistic activity against ERα-SRC1 to inhibit the growth of a breast cancer cell.

摘要

针对细胞内蛋白质-蛋白质相互作用（PPI）的抑制剂的分子设计在药物发现和化学生物学领域备受关注。在此，设计了一种新型环化螺旋-环-螺旋（cHLH）肽，其可抑制雌激素受体α（ERα）与共激活因子SRC1之间的细胞内PPI。该肽cHLH-ERα与ERα结合，并抑制ERα与共激活因子SRC1之间的相互作用。细胞成像和酵母报告基因检测表明，cHLH-ERα可穿透细胞膜，并对ERα-SRC1表现出拮抗活性，从而抑制乳腺癌细胞的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/64815089b91e/CBIC-26-e202500232-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/59878b8a76cd/CBIC-26-e202500232-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/ce8c956ff186/CBIC-26-e202500232-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/64815089b91e/CBIC-26-e202500232-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/59878b8a76cd/CBIC-26-e202500232-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/ce8c956ff186/CBIC-26-e202500232-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/785b/12247020/64815089b91e/CBIC-26-e202500232-g001.jpg

相似文献

1
A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for Cell-Membrane Permeable Inhibitors for the Interaction Between Estrogen Receptor α and Coactivator SRC1.一种环化螺旋-环-螺旋肽作为雌激素受体α与共激活因子SRC1相互作用的细胞膜可渗透抑制剂的分子支架。
Chembiochem. 2025 Jul 11;26(13):e202500232. doi: 10.1002/cbic.202500232. Epub 2025 Jun 20.
2
Timeless Is a Novel Estrogen Receptor Co-activator Involved in Multiple Signaling Pathways in MCF-7 Cells.无时间限制的是一种新型的雌激素受体共激活物，参与 MCF-7 细胞中的多个信号通路。
J Mol Biol. 2018 May 11;430(10):1531-1543. doi: 10.1016/j.jmb.2018.03.008. Epub 2018 Mar 16.
3
Targeted Degradation of the Estrogen Receptor α through Unconventional Coactivator Binding Site (CBS).通过非常规共激活因子结合位点（CBS）靶向降解雌激素受体α
J Med Chem. 2025 Jul 10;68(13):13640-13660. doi: 10.1021/acs.jmedchem.5c00495. Epub 2025 Jun 17.
4
PARP-1 as a novel target in endocrine-resistant breast cancer.聚（ADP-核糖）聚合酶-1作为内分泌抵抗性乳腺癌的新靶点。
J Exp Clin Cancer Res. 2025 Jun 16;44(1):175. doi: 10.1186/s13046-025-03441-4.
5
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.一种环化的螺旋-环-螺旋肽作为分子支架，通过表位和精氨酸嫁接设计细胞内蛋白质-蛋白质相互作用抑制剂。
Angew Chem Int Ed Engl. 2016 Aug 26;55(36):10612-5. doi: 10.1002/anie.201603230. Epub 2016 Jul 28.
6
The steroid receptor coactivator 1 (SRC1) and 3 (SRC3) recruitment as a novel molecular initiating event of 4-n-nonylphenol in estrogen receptor α-mediated pathways.类固醇受体共激活因子 1（SRC1）和 3（SRC3）募集作为 4-壬基酚在雌激素受体 α 介导途径中的新型分子起始事件。
Ecotoxicol Environ Saf. 2020 Feb;189:109958. doi: 10.1016/j.ecoenv.2019.109958. Epub 2019 Nov 22.
7
Cell Membrane Composition Drives Selectivity and Toxicity of Designed Cyclic Helix-Loop-Helix Peptides with Cell Penetrating and Tumor Suppressor Properties.细胞膜组成决定具有细胞穿透和肿瘤抑制特性的设计环螺旋-环螺旋肽的选择性和毒性。
ACS Chem Biol. 2019 Sep 20;14(9):2071-2087. doi: 10.1021/acschembio.9b00593. Epub 2019 Aug 21.
8
Multiple nuclear receptor-regulated endocrine disrupting effects: A case study for bisphenol-induced crosstalk between RARα and ERα signaling pathways.多种核受体调节的内分泌干扰效应：双酚诱导视黄酸受体α（RARα）与雌激素受体α（ERα）信号通路间相互作用的案例研究
J Hazard Mater. 2025 Sep 5;495:139005. doi: 10.1016/j.jhazmat.2025.139005. Epub 2025 Jun 20.
9
Bulk Measurement of Membrane Permeability for Random Cyclic Peptides in Living Cells to Guide Drug Development.活细胞中随机环肽膜通透性的批量测量以指导药物开发
Angew Chem Int Ed Engl. 2025 Jul;64(27):e202500493. doi: 10.1002/anie.202500493. Epub 2025 Jun 1.
10
Regulation of human estrogen receptor alpha-mediated gene transactivation in Saccharomyces cerevisiae by human coactivator and corepressor proteins.人共激活因子和共抑制因子蛋白对酿酒酵母中人类雌激素受体α介导的基因反式激活的调控
J Steroid Biochem Mol Biol. 2007 Feb;103(2):189-95. doi: 10.1016/j.jsbmb.2006.11.001. Epub 2006 Dec 27.

本文引用的文献

1
Stringing along the estrogen receptor to engage with DNA.牵引雌激素受体与DNA结合。
Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2300608120. doi: 10.1073/pnas.2300608120. Epub 2023 Mar 6.
2
New Class of Drug Modalities: Directed Evolution of a De Novo Designed Helix-Loop-Helix Peptide to Bind VEGF for Tumor Growth Inhibition.新型药物模式：从头设计的螺旋-环-螺旋肽的定向进化以结合血管内皮生长因子抑制肿瘤生长
ACS Chem Biol. 2022 Mar 18;17(3):647-653. doi: 10.1021/acschembio.1c00940. Epub 2022 Feb 17.
3
ERα is an RNA-binding protein sustaining tumor cell survival and drug resistance.
雌激素受体α是一种 RNA 结合蛋白，能维持肿瘤细胞的存活和耐药性。
Cell. 2021 Sep 30;184(20):5215-5229.e17. doi: 10.1016/j.cell.2021.08.036. Epub 2021 Sep 23.
4
Structural Basis for α-Helix Mimicry and Inhibition of Protein-Protein Interactions with Oligourea Foldamers.寡脲类分子模拟α-螺旋结构及抑制蛋白-蛋白相互作用的结构基础。
Angew Chem Int Ed Engl. 2021 Feb 1;60(5):2296-2303. doi: 10.1002/anie.202008992. Epub 2020 Dec 1.
5
Construction of reporter gene assays using and mutant yeasts for enhanced detection of various sex steroids.使用[具体名称未给出]和[具体名称未给出]突变酵母构建报告基因检测法以增强对各种性类固醇的检测。
Genes Environ. 2020 May 27;42:20. doi: 10.1186/s41021-020-00159-x. eCollection 2020.
6
An Immune-Stimulatory Helix-Loop-Helix Peptide: Selective Inhibition of CTLA-4-B7 Interaction.一种免疫刺激的螺旋-环-螺旋肽：选择性抑制 CTLA-4-B7 相互作用。
ACS Chem Biol. 2020 Feb 21;15(2):360-368. doi: 10.1021/acschembio.9b00743. Epub 2020 Jan 8.
7
Recent advances in peptidomimetics antagonists targeting estrogen receptor α-coactivator interaction in cancer therapy.靶向雌激素受体α-共激活因子相互作用的拟肽拮抗剂在癌症治疗中的最新进展。
Bioorg Med Chem Lett. 2018 Sep 15;28(17):2827-2836. doi: 10.1016/j.bmcl.2018.05.062. Epub 2018 May 31.
8
Emerging Methods and Design Principles for Cell-Penetrant Peptides.穿细胞肽的新兴方法和设计原则。
Angew Chem Int Ed Engl. 2018 Sep 10;57(37):11868-11881. doi: 10.1002/anie.201801361. Epub 2018 Aug 17.
9
A Cell-Permeable Stapled Peptide Inhibitor of the Estrogen Receptor/Coactivator Interaction.一种细胞可渗透的、稳定化的雌激素受体/共激活因子相互作用肽抑制剂。
ACS Chem Biol. 2018 Mar 16;13(3):676-684. doi: 10.1021/acschembio.7b01016. Epub 2018 Jan 24.
10
Effect of Preorganized Charge-Display on the Cell-Penetrating Properties of Cationic Peptides.预组织电荷分布对阳离子肽细胞穿透性质的影响。
Angew Chem Int Ed Engl. 2017 Jan 2;56(1):122-126. doi: 10.1002/anie.201607649. Epub 2016 Nov 30.