Metal ions modulate the conformation and stability of a G-quadruplex with or without a small-molecule ligand

Huiru Lu, Shenghui Li, Jun Chen, Jing Xia, Jinchao Zhang, Yan Huang, Xiaoxiao Liu, Hai Chen Wu, Yuliang Zhao, Zhifang Chai, Yi Hu

Research output: Contribution to journalArticle

12 Scopus citations

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, Ba2+ 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.

Original languageEnglish (US)
Pages (from-to)1508-1514
Number of pages7
JournalMetallomics
Volume7
Issue number11
DOIs
StatePublished - Nov 2015

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

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