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Structure–Property Relationships in Cu II ‐Binding Tetramolecular G‐Quadruplex DNA
Author(s) -
Engelhard David M.,
Stratmann Lukas M.,
Clever Guido H.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201703409
Subject(s) - linker , ligand (biochemistry) , crystallography , chemistry , copper , stereochemistry , circular dichroism , metal , thermal stability , organic chemistry , biochemistry , receptor , computer science , operating system
A series of artificial metal–base tetrads composed of a Cu II cation coordinating to four pyridines, covalently attached to the ends of tetramolecular G‐quadruplex DNA strands [ L A–D d(G 4 )] 4 ( L A–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 L E with chiral backbone enables incorporation at any oligonucleotide position. We show that ligand chirality distinctly steers Cu II ‐induced G‐quadruplex stabilization. 5′‐End formation of two metal–base tetrads by tetramolecular G‐quadruplex [ L E 2 d(G) 4 ] 4 shows that stabilization in the presence of Cu II is not additive. All results are based on UV/Vis thermal denaturation, thermal difference, circular dichroism experiments and molecular dynamics simulations.