Thermodynamic Properties of the Specific Binding Between Ag⁺Ions and C:C Mismatched Base Pairs in Duplex DNA

Abstract

Metal-mediated base pairs formed by the interaction between metal ions and artificial bases in oligonucleotides have been developed for potential applications in nanotechnology. We recently found that a natural C:C mismatched base pair bound to an Ag(+) ion to generate a novel metal-mediated base pair in duplex DNA. Preparation of the novel C-Ag-C base pair involving natural bases is more convenient than that of metal-mediated base pairs involving artificial bases because time-consuming base synthesis is not required. Here, we examined the thermodynamic properties of the binding between the Ag(+) ion and each of single and double C:C mismatched base pair in duplex DNA by isothermal titration calorimetry. The Ag(+) ion specifically bound to the C:C mismatched base pair at a 1:1 molar ratio with 10(6) M(-1) binding constant, which was significantly larger than those for nonspecific metal ion-DNA interactions. The specific binding between the Ag(+) ion and the single C:C mismatched base pair was mainly driven by the positive dehydration entropy change and the negative binding enthalpy change. In the interaction between the Ag(+) ion and each of the consecutive and interrupted double C:C mismatched base pairs, stoichiometric binding at a 1:1 molar ratio was achieved in each step of the first and second Ag(+) binding. The binding affinity for the second Ag(+) binding was similar to that for the first Ag(+) binding. Stoichiometric binding without interference and negative cooperativity may be favorable for aligning multiple Ag(+) ions in duplex DNA for applications of the metal-mediated base pairs in nanotechnology.

Single Molecule Investigation of Ag+ Interactions with Single Cytosine-, Methylcytosine- and Hydroxymethylcytosine-Cytosine Mismatches in a Nanopore

“…These interactions that strongly stabilize DNA duplexes have been extensively studied recently9, but the nature of coordination of Ag + with C-C mismatches is not clearly understood4101112. Considering that cytosine (C) modifications such as 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) are important epigenetic markers associated with gene expression and tumorigenesis131415, we were motivated to explore the interactions of Ag + with a DNA duplex containing a single C-C, C-mC or C-hmC mismatch in the alpha-hemolysin nanopore (α-HL).…”

Nanolock–Nanopore Facilitated Digital Diagnostics of Cancer Driver Mutation in Tumor Tissue

“…For detection of nucleotide substitutions to C or G, such as the EGFR lung cancer-derived mutation L858R (2573T > G), it is possible to choose the C- or G-involved nanolocks such as the C−Ag−C motif. 34 Recently we have studied C−Ag−C and its application in epigenetic detection in the nanopore. 16 Furthermore, a variety of compounds have been constructed to bind a specific base pair or a group of base pairs.…”

“…Nanolock refers to a sort of nucleic acid motifs that can be formed by binding of ligands such as metal ions 30−34 and designed compounds 35−37 to specific base pairs for stabilization. The sequence specificity of these ligand-bound structures suggests their potential for site-specific detection of genetic alteration.…”

A mini-review on functional nucleic acids-based heavy metal ion detection

“…Much similar to the T-Hg 2+ -T formation, Ag + replaced the imino proton of C residues and leaded to C-Ag + -C formation (Fig. 2 right) with a binding constant in the range of 10 5 M -1 (Torigoe et al, 2011). Besides these Hg 2+ /Ag + -specific DNAs, other heavy metal ions' specific DNAs have also been reported in recent years, for example, Liang et al (2013) designed a G-/T-rich oligonucleotides that selectively recognize Arsenite (As(III)), Zhan et al (2015c) discovered a Cu 2+ -specific ssDNA and Cai et al (2015) modified the streptavidin (SA) aptamer sequence and made it selective to Pt 2+ .…”