Reversible Stabilization of Transition‐Metal‐Binding DNA G‐Quadruplexes

Abstract

You can't top the CopperTop: Tetramolecular G-quadruplexes modified with terminal pyridine ligands exhibit metal-triggered stabilization as monitored by thermal denaturation studies, circular dichroism, and nondenaturing gel electrophoresis. Formation of the square-planar Cu(II) (pyridine)4 complex was confirmed by EPR measurements. The metal complexation is fully reversible by removal of the transition metal with ethylenediaminetetraacetic acid (edta).

Towards Metal-Mediated G-Quartet Analogues: 1,2,4-Triazole Nucleotides

“…The assemblies formed by ON3, ON4, ON5, and ON6 in 100 mM Na + migrated between dT 10 and dT 20 components of the ladder, consistent with literature observations of similar G-quadruplexes. [28] One might expect a noticeable difference in migration rate of G-quadruplexes upon the formation of a metal-coordinating tetrad, [13] however, no metal-dependent changes were observed for any oligonucleotide under these conditions (data not shown).…”

“…It is interesting that a decrease in stability of G-quadruplexes upon addition of Ag + was not as dramatic as for [pyridyl-d(G4)] 4 observed recently ( T 1/2 = −15 • C). [13] This suggests that the coordination mode depicted in Figure 1A does not actually take place and the Ag + interacts with the oligonucleotides by coordination to the 2-position of the triazole rings or to nucleobases.…”

“…Metal-coordinating quartets provide an alternative to the G-tetrad for the design of G-quadruplex assemblies and have recently been demonstrated to increase the thermodynamic stability of the tetramolecular assembly when a coordinating pyridyl group was attached at the 5 -end of dG 3-5 through 1,3-propandiol linker. [13] Here, we report the assembly of tetramolecular G-quadruplexes possessing artificial nucleoside bearing 1,2,4-triazole as a nucleobase ( Figure 1A) in the absence and presence of metal ions. Our experiments revealed that Gquadruplexes are formed by the modified DNA strands but no signs of interaction between the triazole nucleotides and transition metals were detected.…”

“…[9][10][11] We, and others, proposed that a metal-coordinating quartet could function as an orthogonal partner to the standard G-quartet that can guide G-quadruplex formation. [12,13] The concept of metal-coordinating base-pairs in DNA duplexes has been well explored. [14][15][16] The metal-mediated arrangement of DNA triplexes [17,18] and three-way junctions [19] have also been reported.…”

Tailored Transition‐Metal Coordination Environments in Imidazole‐Modified DNA G‐Quadruplexes

“…Previously, this concept was mostly applied in duplex DNA and only a limited number of articles reported about metal‐mediated base interaction in higher secondary structures . Examples include metal‐coordinating triplex DNA, i‐motifs and G‐quadruplex structures . The latter ones assemble from guanine‐rich sequences, in which four guanine residues form planar G‐tetrads through circular Hoogsteen base pairing.…”