Fe^II ₄L₄ tetrahedron binds and aggregates DNA G-quadruplexes

Area of Science:

• Supramolecular Chemistry
• Biochemistry
• Materials Science

Background:

• DNA G-quadruplexes (G4s) are crucial secondary structures in telomeres and other genomic regions, implicated in various biological processes.
• Understanding G4 interactions with external molecules is key to developing novel therapeutic and diagnostic tools.

Purpose of the Study:

• To investigate the binding interaction between a self-assembled tetrahedral metal-organic cage (1) and DNA G-quadruplexes.
• To determine if the metal-organic cage can protect DNA G4s from enzymatic degradation.

Main Methods:

• Fluorescence spectroscopy was used to monitor DNA-cage interactions, observing the quenching of fluorescent labels and G4-selective dyes (thioflavin-T, Zn-PPIX).
• Gel electrophoresis, circular dichroism, and dynamic light scattering were employed to confirm G4-cage binding and characterize aggregate formation.
• S1 nuclease cleavage assays were performed to assess the protective effect of the cage on DNA G4s.

Main Results:

• The metal-organic cage (1) demonstrated binding with a diverse range of DNA G4 sequences.
• Binding led to the formation of aggregate structures, as evidenced by biophysical measurements.
• The cage effectively protected DNA G4s within these aggregates from S1 nuclease degradation.

Conclusions:

• Self-assembled metal-organic cage 1 interacts with and forms aggregates with DNA G-quadruplexes.
• These cage-DNA G4 aggregates provide protection against enzymatic cleavage, suggesting potential applications in G4 stabilization.