Understanding alkali metal cation affinities of multi-layer guanine quadruplex DNA

Abstract

To gain better understanding of the stabilizing interactions between metal ions and DNA quadruplexes, dispersion-corrected density functional theory (DFT-D) based calculations were performed on double-, triple- and four-layer guanine tetrads...

How Divalent Cations Interact with the Internal Channel Site of Guanine Quadruplexes

“…Like previously found for the monovalent alkali metals, [8,9] for the group of divalent alkaline earth metals, the strength of Δ E int is inversely proportional to the ionic radius. In the series Mg 2+ to Ca 2+ to Sr 2+ to Ba 2+ , the steep weakening of Δ E int is mainly determined by less favorable orbital interactions (Δ E oi ), alongside the growth of steric repulsive forces (Δ E Pauli ).…”

“…Ca 2+ has the smallest ionic radius of the Group 2 elements that lie in the center of the two quartet layers, leading to the largest shrinking of the central cavity (Table 1). [21] Mg 2+ is too small to interact with all eight oxygens of the guanine bases simultaneously and resides in the middle of one quartet (Figure 4), as is the case for Li + [8,9] …”

“…Nieuwland et al . showed that the alkali metal cation affinity order observed in double‐layer GQs (K + >Na + >Rb + >Li + ) is preserved in multi‐layer systems as they occur in vivo [9] …”

Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions**

“…[9][10][11] The formation of the tetrad arrangement is accompanied by the accumulation of a quite important negative charge, that could lead to electrostatic repulsion in the center of the quartet, compromising the global stability. For this reason, the central channel is stabilized by the presence of a cation, which leads to a weak electrostatic interaction with the 6-oxygen atoms of the guanines in the tetrad, [12][13][14] usually monovalent alkaline metal ions such as K + and Na + are present. [13] Furthermore, low hydration and crowded environments, such as those found in intracellular conditions, are suitable to increase the G4s stability.…”

Forever Young: Structural Stability of Telomeric Guanine-Quadruplexes in Presence of Oxidative DNA Lesions

“…The formation of the tetrad arrangement is accompanied by the accumulation of a quite important negative charge, that could lead to electrostatic repulsion in the center of the quartet, compromising the global stability. For this reason, the central channel is stabilized by the presence of a cation, which leads to a weak electrostatic interaction with the 6-oxygen atoms of the guanines in the tetrad, 12–14 usually monovalent alkaline metal ions such as K + and Na + . 13 Furthermore, low hydration and crowded environments, such as those found in intracellular conditions, are suitable to increase the G4s stability.…”