环化螺旋-环-螺旋肽作为雌激素受体α与辅激活因子SRC1相互作用的细胞膜渗透性抑制剂的分子支架。

IF 2.6 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

ChemBioChem Pub Date : 2025-05-23 DOI:10.1002/cbic.202500232

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

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引用次数: 0

摘要

细胞内蛋白-蛋白相互作用（PPIs）抑制剂的分子设计对药物发现和化学生物学具有重要意义。在这里，我们设计了一种新的环化螺旋-环-螺旋（cHLH）肽，可以抑制雌激素受体α (ERα)和辅激活因子SRC1之间的细胞内PPI。肽cHLH-ERα结合ERα并抑制ERα与辅激活物SRC1的相互作用。细胞成像和酵母报告细胞实验表明，chhl - er α穿透细胞膜，对ERα-SRC1表现出拮抗活性，抑制乳腺癌细胞的生长。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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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

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.

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来源期刊

ChemBioChem 生物-生化与分子生物学

CiteScore

6.10

自引率

3.10%

发文量

407

审稿时长

1 months

期刊介绍： ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).