期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 24, 期 45, 页码 11785-11794出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201802248
关键词
cancer; DNA binding; heterocycles; metal complexes; polymerase
资金
- UK's Engineering and Physical Sciences Research Council (EPSRC) [EP/H005285/1]
- Royal Society
- British Academy
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.
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