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Artificial metal-base tetrads composed of square-planar Cu II (pyridine) 4 complexes were covalently attached to both the 3' and 5' ends of tetramolecular DNA G-quadruplexes [Ld(G 3-5 )LdT] 4 (L = pyridine ligand) of different lengths. Owing to the planar four-point attachment of the metal complexes, the magnetic orbitals (d x 2 -y 2 ) of the d 9 -configured Cu II cations are placed in a coplanar fashion, separated by the stacked guanine tetrads. Pulsed EPR-derived Cu II -Cu II distances and angles were found to be in agreement with those obtained from molecular dynamics simulations. DNA-confined transition metal spin labels open new ways to study oligonucleotide structure and DNA-protein complexes.

Abstract: A series of artificial metal–base tetrads composed of a CuII cation coordinating to four pyridines, covalently attached to the ends of tetramolecular G‐quadruplex DNA strands [LA–Dd(G4)]4 (LA–D=ligand derivatives), was systematically studied. Structurally, the square‐planar [Cu(pyridine)4] complex behaves analogously to the canonical guanine quartet. Copper coordination to all studied ligand derivatives was found to increase G‐quadruplex thermodynamic stability, tolerating a great variety of ligand linker lengths (1–5 atoms) and thus demonstrating the robustness of the chosen ligand design. Only at long linker lengths, the stabilizing effect of copper binding is compensated by the loss of conformational freedom. A previously reported ligand LE with chiral backbone enables incorporation at any oligonucleotide position. We show that ligand chirality distinctly steers CuII‐induced G‐quadruplex stabilization. 5′‐End formation of two metal–base tetrads by tetramolecular G‐quadruplex [LE2d(G)4]4 shows that stabilization in the presence of CuII is not additive. All results are based on UV/Vis thermal denaturation, thermal difference, circular dichroism experiments and molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

The topological diversity of DNA G-quadruplexes may play a crucial role in its biological function. Reversible control over a specific folding topology was achieved by the synthesis of a chiral, glycol-based pyridine ligand and its fourfold incorporation into human telomeric DNA by solid-phase synthesis. Square-planar coordination to a CuII ion led to the formation of a highly stabilizing intramolecular metal-base tetrad, substituting one G-tetrad in the parent unimolecular G-quadruplex. For the Tetrahymena telomeric repeat, CuII-triggered switching from a hybrid-dominated conformer mixture to an antiparallel topology was observed. CuII-dependent control over a protein-G-quadruplex interaction was shown for the thrombin-tba pair (tba=thrombin-binding aptamer). [ABSTRACT FROM AUTHOR]

Die mit dem Kupferkopf: Mit terminalen Pyridinliganden modifizierte tetramolekulare G ‐ Quadruplexe zeigen metallausgelöste Stabilisierung, wie thermische Denaturierungsstudien, Zirkulardichroismus ‐ Messungen und nichtdenaturierende Gelelektrophorese belegen. Die Bildung des quadratisch ‐ planar koordinierten CuII(Pyridin)4 ‐ Komplexes wurde durch EPR ‐ Messungen bestätigt. Die Komplexierung ist vollständig reversibel durch Entfernen des Übergangsmetalls mit Ethylendiamintetraessigsäure (edta). [ABSTRACT FROM AUTHOR]

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 CuII(pyridine)4 complex was confirmed by EPR measurements. The metal complexation is fully reversible by removal of the transition metal with ethylenediaminetetraacetic acid (edta). [ABSTRACT FROM AUTHOR]