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
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Department of Physiology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
Front Chem. 2021 Nov 9;9:781198. doi: 10.3389/fchem.2021.781198. eCollection 2021.
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.
人们认为G-四链体具有重要的生物学功能，因此已经筛选或开发了许多靶向G-四链体的小分子。然而，找到能够识别特定G-四链体的分子仍然是一个重大挑战。在此，通过结合表面等离子体共振、电喷雾电离质谱、圆二色性、蛋白质免疫印迹、荧光素酶测定和逆转录酶终止测定，我们观察到一种小分子，即氧化苦参碱（OMT），它可以选择性地与人血管内皮生长因子（hVEGF）5'-非翻译区（UTR）中的RNA G-四链体结合，但不能与其他G-四链体结合。OMT可以选择性地抑制宫颈癌细胞中VEGF的翻译。此外，它可以识别特殊构象的VEGF RNA G-四链体。结果表明，OMT可能作为研究细胞中VEGF RNA G-四链体的潜在特殊工具，以及作为设计识别不同G-四链体的配体的有价值支架。
