Different binding mode in AT and GC sequences for unfused-aromatic dications

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Biophysical Chemistry

Background:

• Previously synthesized 2,5-diphenylfuranamidine dication (4) binds AT DNA via minor-groove interaction and GC DNA via intercalation.
• Sequence-dependent DNA binding modes require further investigation, especially for GC-rich sequences.

Purpose of the Study:

• To synthesize and study DNA complexes of novel compounds (1-3) with pyridine, pyrimidine, or triazine central rings.
• To elucidate sequence-dependent DNA binding modes, particularly intercalation into GC-rich DNA.

Main Methods:

• Synthesis of pyridine (1), pyrimidine (2), and triazine (3) analogs.
• Spectroscopic studies (NMR), viscosity measurements, and kinetic analyses of DNA-compound complexes.
• Comparative analysis of binding affinities and modes for AT- and GC-rich DNA sequences.

Main Results:

• Compounds 1-3 bind AT DNA sequences more weakly than furan analog 4, maintaining minor-groove binding.
• Pyridine and pyrimidine derivatives (1, 2) bind GC DNA more strongly than 4; triazine (3) binds more weakly.
• Spectroscopic, viscosity, and kinetic data confirm intercalation into GC sites for compounds 1-4.
• A nonclassical intercalation model explains the GC binding mode of these unfused aromatic compounds.

Conclusions:

• Compounds 1-3 exhibit sequence-dependent DNA binding, interacting with AT and GC sites via distinct mechanisms.
• The findings support a nonclassical intercalation model for unfused aromatic compounds binding to GC-rich DNA.
• This study provides detailed insights into the molecular interactions governing DNA-ligand recognition.