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Binding studies of metal-salphen and metal-bipyridine complexes towards G-quadruplex DNA

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Title: Binding studies of metal-salphen and metal-bipyridine complexes towards G-quadruplex DNA
Authors: Łęczkowska, A
Gonzalez-Garcia, J
Perez-Arnaiz, C
Garcia, B
White, AJP
Vilar, R
Item Type: Journal Article
Abstract: 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 Ni2+ and VO2+ . 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.
Issue Date: 1-Aug-2018
Date of Acceptance: 4-May-2018
URI: http://hdl.handle.net/10044/1/61457
DOI: https://dx.doi.org/10.1002/chem.201802248
ISSN: 0947-6539
Publisher: Wiley
Start Page: 11785
End Page: 11794
Journal / Book Title: Chemistry - A European Journal
Volume: 24
Issue: 45
Copyright Statement: © 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the pre-peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201802248
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
cancer
DNA binding
heterocycles
metal complexes
polymerase
SQUARE-PLANAR
STABILIZATION
TELOMERASE
INHIBITION
CONSTANTS
DNA binding
cancer
heterocycles
metal complexes
polymerase
2,2'-Dipyridyl
Coordination Complexes
Crystallography, X-Ray
G-Quadruplexes
Humans
Ligands
Phenylenediamines
Promoter Regions, Genetic
Telomere
Telomere
Humans
Phenylenediamines
2,2'-Dipyridyl
Ligands
Crystallography, X-Ray
G-Quadruplexes
Promoter Regions, Genetic
Coordination Complexes
DNA binding
cancer
heterocycles
metal complexes
polymerase
03 Chemical Sciences
General Chemistry
Publication Status: Published
Conference Place: Germany
Online Publication Date: 2018-06-13
Appears in Collections:Chemistry
Biological and Biophysical Chemistry
Faculty of Natural Sciences



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