G-quadruplex-based structural transitions in 15-mer DNA oligonucleotides varying in lengths of internal oligo(dG) stretches detected by voltammetric techniques

Abstract

Electrochemical methods, particularly when applied in connection with mercury-containing electrodes, are excellent tools for studying nucleic acids structure and monitoring structural transitions. We studied the effect of the length of the central (dG) n stretch (varying from 0 to 15 guanine residues) in 15-mer oligodeoxynucleotides (ODN, G0 to G15) on their electrochemical and interfacial behavior at mercury and carbon electrodes. The intensity of guanine oxidation signal at the carbon electrode (peak G(ox)) was observed to increase continuously with number of guanines between 0 and 15, with only a slight positive shift for ODNs with seven or more guanines in the central segment. Very different effects were observed when the peak G(HMDE) was measured at the mercury electrode. Intensity of the latter signal increased with number of guanines up to G5, and decreased sharply with further elongation of the (dG) n stretch. CD spectroscopy and electrophoresis experiments revealed formation of parallel intermolecular quadruplex structures for ODNs containing five or more G residues. Further measurements made by cyclic and alternating-current voltammetry revealed a strong influence of the ODN structure on their behavior at electrically charged surfaces.

Hydrogen Evolution Facilitates Reduction of DNA Guanine Residues at the Hanging Mercury Drop Electrode: Evidence for a Chemical Mechanism

“…B). To observe this well developed, symmetrical and analytically useful signal, cyclic voltammetry (CV) with properly set negative vertex potential (in AFP at −1.85 V) has most frequently been used –. Alternatively, square wave voltammetry or constant current chronopotentiometry , with initial potential sufficiently negative to allow G reduction, were applied.…”

“…A), damage of this moiety causes the peak G to diminish . More recently we have shown that formation of alternative DNA structures, particularly G quadruplexes in which the G imidazole ring is involved in Hoogsteen base pairing, is reflected in reduced intensity of the peak G, compared to unstructured or even to the canonical duplex DNA .…”

Electrochemical behavior of 7-deazaguanine- and 7-deazaadenine-modified DNA at the hanging mercury drop electrode

“…Electrochemical responses of NAs are sensitive to changes in the DNA structure (which applies particularly to those measured at the mercury and some types of amalgam or mercury film electrodes [3,4]), making it possible to detect not only DNA denaturation, but also more subtle structural changes such as those related to DNA superhelicity [5], formation of single-or double-strand breaks [6] and so forth, using solely intrinsic DNA signals. Other structural transitions, involving formation of DNA triple helices [7] or quadruplexes [8,9], have recently been detected using label-free electrochemical methods as well.…”

Label‐free Voltammetric Detection of Products of Terminal Deoxynucleotidyl Transferase Tailing Reaction

“…For the tailing reaction, three types of homooligonucleotides – A 30 , C 30 and T 30 – were used as primers to which various dNTPs (dATP, dCTP, dGTP, dTTP, 7‐deazaadenine – dA*TP and 7‐deazaguanine – dG*TP or their combinations) were added to form the tail. G 30 was not used as a primer since DNA oligonucleotides containing longer stretches of guanines tend to form G‐quadruplexes (G4) and such structure would not be a suitable substrate for TdT because of its inability to access the 3′‐OH end folded within the G4 structure. Figure shows cyclic voltammograms at HMDE and square wave voltammograms at PGE gained for the A 30 , C 30 and T 30 primers compared to blank electrolyte.…”

“…Moreover, adsorption/desorption processes or reorientation of parts of the DNA chains occur at the negatively charged surface of mercury electrodes, which can be observed as tensammetric (capacitive) signals . Generally, signals gained at mercury‐containing electrodes are remarkably sensitive to changes in DNA structure, which enables detection of different types of changes, such as formation of strand breaks , DNA superhelicity‐induced structural transitions , binding of DNA intercalators or formation of non‐canonical DNA structures such as triplexes and quadruplexes .…”