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Binding Studies of Metal–Salphen and Metal–Bipyridine Complexes towards G‐Quadruplex DNA
Author(s) -
Łęczkowska Anna,
GonzalezGarcia Jorge,
PerezArnaiz Cristina,
Garcia Begoña,
White Andrew J. P.,
Vilar Ramon
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.201802248
Subject(s) - metal , bipyridine , chemistry , dna , combinatorial chemistry , crystallography , biochemistry , organic chemistry , crystal structure
The proposed in vivo formation of G‐quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di‐substituted bipyridine ligand and the corresponding complexes with Ni 2+ and VO 2+ . Both these new complexes have been characterized spectroscopically and by X‐ray crystallography. Detailed DNA binding studies of these two complexes, together with three previously reported metal salphen complexes, are presented. Using FRET melting assays, the binding affinity and selectivity of the five metal complexes against six different G4 DNA structures as well as a duplex DNA have been determined. In addition, we present detailed ITC and UV/Vis studies to characterize the interaction of the complexes with human telomeric G4 DNA. Finally, we show via a polymerase stop assay that these complexes are able to stabilize a G4 DNA structure (from the c‐Myc oncogene promoter) and halt the activity of Taq polymerase.