A novel square-planar Pt(ii) complex as a monomeric and dimeric G-quadruplex DNA binder

Area of Science:

• Medicinal Chemistry
• Biochemistry
• Molecular Biology

Background:

• G-quadruplexes (G4) are non-canonical DNA structures implicated in various biological processes.
• Targeting specific G4 topologies is crucial for developing selective therapeutic agents.

Purpose of the Study:

• To synthesize and characterize a novel platinum(II) complex with a phenanthroimidazole ethylenediamine core and a coumarin derivative.
• To investigate the binding affinity, selectivity, and thermal stabilization properties of the complex towards different DNA structures, particularly G-quadruplexes.

Main Methods:

• Synthesis and characterization of the platinum(II) complex.
• DNA-binding studies using techniques like UV-Vis titration, fluorescence spectroscopy, and thermal denaturation assays.
• Selectivity assays comparing binding to dimeric G-quadruplexes (G2T1), monomeric G-quadruplexes (G1), and duplex DNA.

Main Results:

• The novel platinum(II) complex (1) was successfully synthesized.
• Complex 1 exhibited higher binding affinity and selectivity for mixed-type dimeric G-quadruplexes (G2T1) compared to monomeric G-quadruplexes (G1) and duplex DNA.
• The complex demonstrated significant thermal stabilization of the targeted G-quadruplex structures.
• Binding modes were identified as end-stacking and external binding to G-quadruplexes.

Conclusions:

• The synthesized platinum(II) complex displays remarkable selectivity for dimeric G-quadruplexes.
• Complex 1 shows potential as a selective G-quadruplex targeting agent due to its high affinity and stabilizing effects.