A Recognization Of Natural Compounds Towards To DNA G-quadruplexes And Duplexes By ESI-MS

In addition to duplex DNA, Guanine-rich DNA sequences can fold into four-stranded structures, called G-quadruplexes. Telomeres are DNA-protein structures consisting of repeated TTAGGG sequences at the end of the chromosome., which is responsible for genome integrity and protects chromosomes from damage and recombination. The G-quadruplexes formed by the single chain in G-rich field of telomere 3'end prohibit the activity of telomerase resulting in tumor cell apoptosis. Telomerase is a characteristic reverse transcriptase containing an endogenous RNA template and protein components, and it has been conformed that elevated levels of telomerase expression were found in 85-90% of human tumor cells, while they were not detect able in normal somatic cells. Telomerase can inhibit the shortening of telomere and stimulate continuous cell proliferation to form tumor. Ligands that selectively bind to G-quadruplex structures may interfere with telomere elongation and replication of cancer cells, therefore have potential uses for the cure of cancer. As various G-quadruplex sequences in the promoter regions or telomeres can form different secondary structural modes and display a diversity of biology functions, variant G-quadruplex interactive agents may be necessary to cure different disease by differentiating variant types of G-quadruplexes. Here we extend our study to ESI-MS measurements of the affinity of natural compounds towards different DNA structures, with particular attention to the selectivity shown for G-quadruplex over duplex DNA.Tea is one of the most popular beverages worldwide. Among the biological activities of tea, the cancer-preventive activity has attracted the greatest attention. Among the green tea constituents, (-)-epigallocatechin-3- gallate (EGCG) is the most abundant and most active constituent in inhibiting experimental carcinogenesis and related reactions. Much of the mechanistic information on the possible biological activities of tea was derived from studies in cell lines with EGCG. Nevertheless, the exact mechanisms underlying these activities are still elusive and mostly speculative. Here, mass spectrometry was used to determine the affinity of EGCG for DNA structures among quadruplexes and duplexes. Our data confirm that EGCG exhibit a significant preference for quadruplexes over duplexes. This is the first report on the recognition of EGCG with polymorphism of G-quadruplex, which suggests that EGCG potentially exhibit the role of inhibition of telomerase activity, it can provide important guidance to explore new clinic studies of EGCG drugs. EGCG could be a stronger quadruplex ligand and therefore a stronger telomerase inhibition.Flavonoids, an important class of natural products, present abundantly in fruits and vegetables. Flavonoids consist of a diverse group of compounds such as flavone, flavonol, flavanone as well as isoflavone, and are known to have many biological functions beneficial to human health. The interactions of flavonoids with nucleic acid structures play an important role in mechanism of their actions. Moreover, there is growing evidence for flavonoids with a wide range of therapeutic activities against cancers, tumors, etc. For these reasons, the noncovalent interactions between flavonoids and G-quadruplex DNA have attracted considerable interest and have been investigated. In this study, the interaction between rutin, quercetin, naringin, puerarin and G-quadruplex DNA has been investigated by ESI-MS.