Mechanism of the hairpin folding transformation of thymine-cytosine-rich oligonucleotides induced by Hg(II) and Ag(I) ions

Abstract

The metal-induced folding of thymine-cytosine-rich oligonucleotides into hairpin-like structures was characterised by isothermal titration calorimetry, secondary structure analysis, equilibrium titrations, and fluorescence study. We find that designed thymine-cytosine-rich oligonucleotides can specifically bind with Hg(II) or Ag(I) ions to generate metal-mediated base pairs in a hairpin-like structure from a random coil structure. Isothermal titration calorimetry experiments were performed to reveal the detail of the whole binding process. The thermodynamic result exhibits two possible pathways of significant change upon the addition of Hg(II) ions. Furthermore, this transformation can be enhanced by the presence of Ag(I) ions. The fluorescence decreases through fluorescence resonance energy transfer (FRET) between the fluorophore and quencher confirms the process of formation of the hairpin-like structure. The analysis of optical titration data demonstrates that the saturated binding stoichiometries are 12:1 and 4:1 for Hg(II) and Ag(I) ions, respectively. Our result provides a promising strategy for the investigation of the mechanism of structural transformation of oligonucleotides influenced by metal-mediated base pairs, which may eventually lead to progress in constructing a metal-triggered DNA origami system and metal-containing DNA nanotechnology.