title: G-Quadruplex binding enantiomers show chiral selective interactions with human telomere.
abstract: Chiral recognition of DNA molecules is important because DNA chiral transition and its different conformations are involved in a series of important life events. Among them, polymorphic human telomere DNA has attracted great interests in recent years because of its important roles in chromosome structural integrity. In this report, we examine the short-term effect of chiral metallo-supramolecular complex enantiomers treatment on tumor cells, and find that a zinc-finger-like alpha helical chiral metallo-supramolecular complex, [Ni2L3](4+)-P enantiomer (NiP), can selectively provoke the rapid telomere uncapping, trigger DNA damage responses at telomere and degradation of G-overhang and the delocalization of telomeric protein from telomeres. Further studies indicate that NiP can induce an acute cellular apoptosis and senescence in cancer cells rather than normal cells. These results are further evidenced by the upregulation of p21 and p16 proteins. Moreover, NiP can cause translocation of hTERT from nuclear to cytoplasm through Tyr 707 phosphorylation. While its enantiomer, [Ni2L3](4+)-M (NiM), has no such mentioned effects, these results clearly demonstrate the compound's chiral selectivity in cancer cells. Our work will shed light on design of chiral anticancer drugs targeting G-quadruplex DNA, and developing telomere and telomerase modulation agents.
authors.affiliation: Laboratory of Chemical Biology, Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Changchun, Jilin 130022, China, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, Jilin 130022, China and Department of Neurosurgery, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Jiasi
authors.initials: J
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ren
authors.forename: Chuanqi
authors.initials: C
authors.lastname: Zhao
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Qu
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D007536:Isomerism; D061986:MCF-7 Cells; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D034501:Telomere-Binding Proteins; D004247:DNA