The involvement of non-canonical DNA structures, such as G-quadruplex (G4) DNA, in cancer development and progression has set the pace towards the renaissance of DNA-binding metal complexes. In this work, we report the DNA-binding of three Ni(II), Cu(II), Zn(II) complexes of a salphen-like N4-donor ligand, bearing two imidazole groups condensed with a phenylenediamine moiety. Both duplex and G4 DNAs derived from human telomeres (hTelo), and a sequence mimicking the promoter of the oncogene myc (c-myc) were studied. UV-Vis and circular dichroism spectroscopic binding studies pointed out that, while all the three complexes bind the selected oligonucleotides, the Cu(II) derivative is the strongest and G4-selective compound of the series. Lastly, FRET DNA melting assay results on the Cu(II) complex/hTelo G4 system were interpreted by a loop-binding mechanism of interaction, as corroborated by molecular dynamics (MD) simulations.

On the G-Quadruplex Binding of a New Class of Nickel(II), Copper(II), and Zinc(II) Salphen-Like Complexes

Santoro A.;Bruno G.;
2021-01-01

Abstract

The involvement of non-canonical DNA structures, such as G-quadruplex (G4) DNA, in cancer development and progression has set the pace towards the renaissance of DNA-binding metal complexes. In this work, we report the DNA-binding of three Ni(II), Cu(II), Zn(II) complexes of a salphen-like N4-donor ligand, bearing two imidazole groups condensed with a phenylenediamine moiety. Both duplex and G4 DNAs derived from human telomeres (hTelo), and a sequence mimicking the promoter of the oncogene myc (c-myc) were studied. UV-Vis and circular dichroism spectroscopic binding studies pointed out that, while all the three complexes bind the selected oligonucleotides, the Cu(II) derivative is the strongest and G4-selective compound of the series. Lastly, FRET DNA melting assay results on the Cu(II) complex/hTelo G4 system were interpreted by a loop-binding mechanism of interaction, as corroborated by molecular dynamics (MD) simulations.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3230592
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