title: Metal ions modulate the conformation and stability of a G-quadruplex with or without a small-molecule ligand.
abstract: Small-molecule ligands for stabilizing the G-quadruplex in telomeres are promising chemotherapeutic agents. Despite extensive research, few G-quadruplex-stabilizing ligands have been clinically approved to date. We hypothesized that metal ions may be able to interfere with the ligand-mediated stabilization of the G-quadruplex. Here we found that several metal ions could interfere with the Na(+)-induced G-quadruplex conformation even in the presence of a ligand. The destabilizing effects of metal ions may not be negligible as most of them are essential elements in organisms. In contrast, Ba(2+) was found to be a potent stabilizing cation, which could compete with other destabilizing cations to modulate the stability of the G-quadruplex. Moreover, the destabilizing effects of divalent or trivalent cations were considerably inhibited when a metal chelator was used. These data suggested that the unfavorable effects of destabilizing cations must be minimized for enhancing the ligand-mediated stabilization of the G-quadruplex.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, China. huyi@ihep.ac.cn.
authors.forename: Huiru
authors.initials: H
authors.lastname: Lu
authors.forename: Shenghui
authors.initials: S
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Liu
authors.forename: Hai-chen
authors.initials: HC
authors.lastname: Wu
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Chai
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D019216:Metals, Heavy / Q000737:chemistry* / Q000494:pharmacology*; D009690:Nucleic Acid Conformation
chemical_list: D008024:Ligands; D019216:Metals, Heavy; D004247:DNA