Photoswitchable agonists for visible-light activation of the Wnt signaling pathway†

IF 2.7 3区 化学 Q1 CHEMISTRY, ORGANIC Organic & Biomolecular Chemistry Pub Date : 2025-03-24 DOI:10.1039/d4ob01827c
Shifa Ahmad , P. K. Hashim , Masamichi Imajo , Nusaiba Madappuram Cheruthu , Kiyonori Takahashi , Shinya Tanaka , Takayoshi Nakamura , Nobuyuki Tamaoki
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Abstract

Based on the known Wnt agonist , we designed and synthesized photoswitchable azo derivative compounds that can act as agonists for the Wnt signaling pathway. These photoswitchable agonists were shown to undergo reversible transcis isomerization upon being irradiated with visible light, but only the cis isomer was observed to activate the Wnt signaling pathway, using a luminescense-based reporter assay in cultured cells. One of the compounds, denoted as compound , showed ∼88% agonist activity after being subjected to visible light irradiation in comparison to the non-photoswitchable . We also were able to selectively activate the Wnt signaling pathway using and light irradiation at a specific region of interest in a model cell culture system, highlighting the ability to achieve spatiotemporal regulation.

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可见光激活Wnt信号通路的光切换激动剂。
基于已知的Wnt激动剂BML-284,我们设计并合成了可作为Wnt信号通路激动剂的光切换偶氮衍生物。这些光切换激动剂被证明在可见光照射下发生可逆的反式顺式异构化,但在培养细胞中使用基于发光的报告细胞实验,仅观察到顺式异构体激活Wnt信号通路。其中一种化合物,标记为化合物2,与不可光切换的BML-284相比,在可见光照射下显示出约88%的激动剂活性。我们还能够在模型细胞培养系统的特定区域使用2和光照射选择性激活Wnt信号通路,突出了实现时空调节的能力。
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来源期刊
Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry 化学-有机化学
CiteScore
5.50
自引率
9.40%
发文量
1056
审稿时长
1.3 months
期刊介绍: Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.
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