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.
