Stężycka Olga, Frańska Magdalena, Nowak Damian, Hoffmann Marcin, Kasperkowiak Małgorzata, Beszterda-Buszczak Monika
Institute of Chemistry and Technical Electrochemistry, Poznań University of Technology, Berdychowo 4, 60-965 Poznań, Poland.
Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.
Int J Mol Sci. 2025 May 1;26(9):4312. doi: 10.3390/ijms26094312.
Polyphenols make a numerous and diverse group of plant secondary metabolites exhibiting remarkable anticancer activities, often attributed to their G-quadruplex binding properties. Therefore, there is a need to develop a high-throughput screening assay which would permit the evaluation of polyphenols' binding properties toward G-quadruplex. As deoxyguanosine and guanosine are essential and key building blocks of G-quadruplexes, the stabilities of their adducts with polyphenols may reflect the stabilities of polyphenols-G-quadruplex adducts. In this study, deoxyguanosine/guanosine post-column addition experiments have been performed during HPLC-MS analysis of extract. The stabilities of the deoxyguanosine/guanosine adducts with 3--methylquercetin-7--glucoside, 4'-hydroxydehydrokawain-4'--glucoside, and 3,5-di--caffeoylquinic acid-compounds identified in the extract-have been tested by using collision-induced dissociation 'in-source'. The obtained results show that the identified compounds form more stable adducts with deoxyguanosine and guanosine than the standards used for comparison, namely isoquercitrin and rutin. The performed molecular docking provided some insight into the structure of the adducts and revealed that multiple interactions are of key importance for their stabilities.
多酚是一类数量众多、种类多样的植物次生代谢产物，具有显著的抗癌活性，其抗癌活性通常归因于它们与G-四链体的结合特性。因此，需要开发一种高通量筛选方法，以评估多酚对G-四链体的结合特性。由于脱氧鸟苷和鸟苷是G-四链体的重要组成部分，它们与多酚形成的加合物的稳定性可能反映多酚-G-四链体加合物的稳定性。在本研究中，在提取物的高效液相色谱-质谱分析过程中进行了脱氧鸟苷/鸟苷柱后添加实验。通过“源内”碰撞诱导解离测试了脱氧鸟苷/鸟苷与提取物中鉴定出的3 - 甲基槲皮素-7 - 葡萄糖苷、4'-羟基脱氢卡瓦因-4'-葡萄糖苷和3,5-二 - 咖啡酰奎尼酸化合物形成的加合物的稳定性。所得结果表明，与用于比较的标准品异槲皮苷和芦丁相比，鉴定出的化合物与脱氧鸟苷和鸟苷形成的加合物更稳定。所进行的分子对接为加合物的结构提供了一些见解，并揭示了多种相互作用对其稳定性至关重要。
