Structure-Property Relationships in CuII -Binding Tetramolecular G-Quadruplex DNA.
Chemistry
; 24(9): 2117-2125, 2018 Feb 09.
Article
em En
| MEDLINE
| ID: mdl-29139578
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-D d(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 [LE2 d(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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cobre
/
Quadruplex G
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha