Research On Regulation Of Conformation Of G-quadruplex And Interaction With Ligands

Tumor is a serious common and frequently-occurring disease,has now become the second disease that cause human deaths, is one ofthe most difficult to treat and the most to invest..Studies have shown thatsmall molecular ligandscan induc sequence of high G DNA to or help toform stable G-quadruplex structure that can inhibit telomerase activity orlower cancer gene transcription and inhibite tumor.This thesis, we use theflavonoids interact with G-quadruplex, and then use electric chemistrymethod to examine the interaction, then through simulation to calculatethe size of the binding energy. The main results obtained are listed asfollows:(1) characterization of flavonoids (apigenin, rutin, quercetin),such as: mass spectrometry, nuclear magnetic resonance (1H,13C) andinfrared characterization methods to confirm its structure, in order tobetterunderstand the interaction between DNA and ligands.(2) Use electricity chemical methods such like electrochemicalimpedance spectroscopy, cyclic voltammetry to study interaction between flavonoids and G-quadruplex(3) Use AutoDock simulation means to simulate interactionbetween the DNA and flavonoids, confirmed its connection mode (suchas big groove, small grooves, apex or low-end, or both). Through theexperiment and simulation comparison, our final confirmation:Binding energy between apigenin and G-quadruplex:-8.20kcal/mol,size of interaction is1.26×104M-1,Combination is embeddedmode.Binding energy between quercetin and G-quadruplex:-6.90kcal/mol,size of interaction is9.42×103M-1,Combination is Groovebinding.Binding energy between apigenin and G-quadruplex:-3.17kcal/mol,size of interaction is1.56×104M-1,Combination is embeddedmode.