AUTHOR=Hu Xiao-Xia , Wang Sheng-Quan , Gan Shi-Quan , Liu Lei , Zhong Ming-Qing , Jia Meng-Hao , Jiang Fei , Xu Yan , Xiao Chao-Da , Shen Xiang-Chun 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 JOURNAL=Frontiers in Chemistry VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.781198 DOI=10.3389/fchem.2021.781198 ISSN=2296-2646 ABSTRACT=

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.