A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation
G-quadruplexes are believed to have important biological functions, so many small molecules have been screened or developed for targeting G-quadruplexes. However, it is still a major challenge to find molecules that recognize specific G-quadruplexes. Here, by using a combination of surface plasmon r...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2021.781198/full |
| _version_ | 1819015837457055744 |
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| author | Xiao-Xia Hu Xiao-Xia Hu Sheng-Quan Wang Shi-Quan Gan Lei Liu Ming-Qing Zhong Meng-Hao Jia Fei Jiang Yan Xu Chao-Da Xiao Chao-Da Xiao Xiang-Chun Shen Xiang-Chun Shen |
| author_facet | Xiao-Xia Hu Xiao-Xia Hu Sheng-Quan Wang Shi-Quan Gan Lei Liu Ming-Qing Zhong Meng-Hao Jia Fei Jiang Yan Xu Chao-Da Xiao Chao-Da Xiao Xiang-Chun Shen Xiang-Chun Shen |
| author_sort | Xiao-Xia Hu |
| collection | DOAJ |
| description | G-quadruplexes are believed to have important biological functions, so many small molecules have been screened or developed for targeting G-quadruplexes. However, it is still a major challenge to find molecules that recognize specific G-quadruplexes. Here, by using a combination of surface plasmon resonance, electrospray ionization mass spectrometry, circular dichroism, Western blot, luciferase assay, and reverse transcriptase stop assay, we observed a small molecule, namely, oxymatrine (OMT) that could selectively bind to the RNA G-quadruplex in 5′-untranslated regions (UTRs) of human vascular endothelial growth factor (hVEGF), but could not bind to other G-quadruplexes. OMT could selectively repress the translation of VEGF in cervical cancer cells. Furthermore, it could recognize VEGF RNA G-quadruplexes in special conformations. The results indicate that OMT may serve as a potentially special tool for studying the VEGF RNA G-quadruplex in cells and as a valuable scaffold for the design of ligands that recognize different G-quadruplexes. |
| first_indexed | 2024-12-21T02:38:05Z |
| format | Article |
| id | doaj.art-2f20155105b643479e8d937b51fb43c4 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-21T02:38:05Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-2f20155105b643479e8d937b51fb43c42022-12-21T19:18:45ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-11-01910.3389/fchem.2021.781198781198A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the TranslationXiao-Xia Hu0Xiao-Xia Hu1Sheng-Quan Wang2Shi-Quan Gan3Lei Liu4Ming-Qing Zhong5Meng-Hao Jia6Fei Jiang7Yan Xu8Chao-Da Xiao9Chao-Da Xiao10Xiang-Chun Shen11Xiang-Chun Shen12State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaDepartment of Physiology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaDivision of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki, JapanState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaThe Key Laboratory of Optimal Utilization of Natural Medicine Resources, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang,ChinaThe Key Laboratory of Optimal Utilization of Natural Medicine Resources, Guizhou Medical University, Guiyang, ChinaG-quadruplexes are believed to have important biological functions, so many small molecules have been screened or developed for targeting G-quadruplexes. However, it is still a major challenge to find molecules that recognize specific G-quadruplexes. Here, by using a combination of surface plasmon resonance, electrospray ionization mass spectrometry, circular dichroism, Western blot, luciferase assay, and reverse transcriptase stop assay, we observed a small molecule, namely, oxymatrine (OMT) that could selectively bind to the RNA G-quadruplex in 5′-untranslated regions (UTRs) of human vascular endothelial growth factor (hVEGF), but could not bind to other G-quadruplexes. OMT could selectively repress the translation of VEGF in cervical cancer cells. Furthermore, it could recognize VEGF RNA G-quadruplexes in special conformations. The results indicate that OMT may serve as a potentially special tool for studying the VEGF RNA G-quadruplex in cells and as a valuable scaffold for the design of ligands that recognize different G-quadruplexes.https://www.frontiersin.org/articles/10.3389/fchem.2021.781198/fullG-quadruplexVEGFselective ligandtranslationRNA |
| spellingShingle | Xiao-Xia Hu Xiao-Xia Hu Sheng-Quan Wang Shi-Quan Gan Lei Liu Ming-Qing Zhong Meng-Hao Jia Fei Jiang Yan Xu Chao-Da Xiao Chao-Da Xiao Xiang-Chun Shen Xiang-Chun Shen A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation Frontiers in Chemistry G-quadruplex VEGF selective ligand translation RNA |
| title | A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation |
| title_full | A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation |
| title_fullStr | A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation |
| title_full_unstemmed | A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation |
| title_short | A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation |
| title_sort | small ligand that selectively binds to the g quadruplex at the human vascular endothelial growth factor internal ribosomal entry site and represses the translation |
| topic | G-quadruplex VEGF selective ligand translation RNA |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2021.781198/full |
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