The formation of G-quadruplex in biologically relevant DNA sequences induced by alkaloid

摘要

Many Guanine-rich DNA sequences are capable of forming G-quadruplex, such as the telomeric chromosomal terminals and the promoters of several genes including c-myc, c-kit and bcl-2 oncogenes. G-quadruplex structure have conspicuous biological significance and hence the ligands which can promote the formation and stabilize G-quadruplex have attracted much attention. In this paper, we have evaluated the abilities of Jatrorrhizine and Chelerythrine in inducing the formation of G-quadruplex employing Circular Dichroism spectroscopy. Our results indicate that Jatrorrhizine can induce Pu18 and c-kit87up to form mixed-type and parallel G-quadruplex respectively. Chelerythrine can induce Pu18 and c-kit87up to form parallel and antiparallel G-quadruplex respectively. Jatrorrhizine and Chelerythrine can induce the switch of Pu18 G-quadruplex in the presence of K⁺ from mixed-type to antiparallel and parallel respectively. However, Jatrorrhizine and Chelerythrine can not change the conformation of c-kit87up G-quadruplex in the presence of K⁺. From experimental results it is clear that Jatrorrhizine and Chelerythrine may have the potential to inhibit the growth of tumour cell and also can be useful guidelines for the design of anticancer agents.