Ferrocenyl naphthalene diimides as tetraplex DNA binders

Area of Science:

• Supramolecular Chemistry
• Medicinal Chemistry
• Biophysical Chemistry

Background:

• Tetraplex DNA structures, including telomeric DNA, play crucial roles in cellular processes.
• Developing selective ligands for tetraplex DNA is essential for understanding its function and for therapeutic development.
• Ferrocenyl naphthalene diimide (FND) derivatives are explored as potential DNA-binding agents.

Purpose of the Study:

• To synthesize and characterize novel ferrocenyl naphthalene diimide (FND) ligands.
• To evaluate the binding affinity and selectivity of these FNDs towards tetraplex DNA compared to single- and double-stranded DNA.
• To assess the potential of FNDs to modulate the activity of enzymes like telomerase and Taq polymerase.

Main Methods:

• Synthesis of seven distinct FND ligands.
• Electrochemical methods to quantify binding affinities to immobilized tetraplex DNA.
• Spectroscopic techniques to confirm DNA-ligand interactions.
• Telomerase repeat amplification protocol (TRAP) assay to evaluate enzyme inhibition.

Main Results:

• All seven synthesized FND ligands demonstrated higher affinity for tetraplex DNA than for single- or double-stranded DNA.
• Binding affinities for tetraplex DNA were found to be greater than 10^5 M^-1 under specified buffer conditions.
• The most effective FND ligands exhibited 23-fold and 8-fold selectivity for tetraplex DNA over single- and double-stranded DNA, respectively.
• Electrochemical signals correlated with FND binding affinities to tetraplex DNA.
• FND ligands were classified into three groups based on their differential inhibition of telomerase and Taq polymerase.

Conclusions:

• Ferrocenyl naphthalene diimide (FND) ligands are effective binders of tetraplex DNA with high selectivity.
• The binding affinity of FNDs to tetraplex DNA can be modulated by structural modifications.
• FNDs demonstrate potential as inhibitors of telomerase, suggesting applications in cancer therapy or diagnostics.