Study On Interactions Of Curcumin And Daidzin With DNA G-quadruplex

Telomeres, the end of eukaryote chromosomes, contain guanine-rich DNAsequences. Telomere erosion occurs naturally during replication of somatic cells.These cells continue to function and divide until a critically short length oftelomeric DNA is reached, when cells enter a stage of irreversible growth arrest,replicative senescence, followed by cell crisis and apoptosis. Tumor cell'stelomeres are maintained in length so that they are effectively immortalized.Guanine-rich DNA sequences have the ability to form four stranded inter-andintramolecular guanine quadruplex structures under conditions of high sodium orpotassium ionic strength. Since the RNA template of telomerase requires a nofolded telomeric DNA primer in order to affect telomere synthesis, the formation oftelomeric G-quartet structure at high potassium ion levels results in the inhibitionof telomerase function. A number of small molecules have been discovered toinhibit the function of telomerase. So G-quadruplex is a potential target foranticancer.By using Ultraviolet (UV) and Circular Dichroism (CD) spectroscopy andElectrospray Ionization Mass Spectrometry (ESI-MS) we study the curcumin affectthe structure and stability of G-quadruplex formed from 5'-G₄T₄G₄-3' and doublestrands DNA formed from 5'-G₄T-4G₄-3' and its complement in different buffers.We study the curcumin interact G-quadruplex formed from 5'-G₄T₄G₄-3' in thecrowding condition too. Then we use SYBYL 6.90 software to study curcumin anddaidzin interact G-quadruplex. In addition, we study curcumin and daidzin interactG-quadruplex formed from 5'-AGGG(TTAGGG)3-3' in the weak solution andcrowding condition.The results indicate that the curcumin can't combine with G-quadruplexformed from 5'-G₄T₄G₄-3' and 5'-AGGG(TTAGGG)3-3' in weak solution. Incrowding condition, curcumin can't combine with G-quadruplex formed from5'-AGGG(TTAGGG)3-3' but can combine with G-quadruplex formed from5'-G₄T₄G₄-3' and improve the G-quadruplex stability. The daidzin can combinewith G-quadruplex formed from 5'-G₄T₄G₄-3' with stoichiometric proportion 2:1 or1:1, and with G-quadruplex formed from 5'-AGGG(TTAGGG)3-3' withstoichiometric proportion 1:1, at the same time improves the stability ofG-quadruplexes. In crowding condition, the daidzin can combine withG-quadruplex and improves the G-quadruplexes greatly. The result of simulationindicate that the ability of daidzin combining with G-quadruplex formed from5'-G₄T₄G₄-3' stronger than curcumin's, which conform with the results ofexperiment.