Supramolecular polymer formation by cyclic dinucleotides and intercalators affects dinucleotide enzymatic processing.

Area of Science:

• Biochemistry
• Materials Science
• Nanotechnology

Background:

• Cyclic dinucleotides form supramolecular aggregates with intercalators.
• This property has potential applications in nanotechnology and medicine.

Purpose of the Study:

• To investigate the formation and properties of cyclic dinucleotide-intercalator complexes.
• To explore the stability and potential applications of these supramolecular structures.

Main Methods:

• Atomic force microscopy (AFM) to visualize G-wire formation.
• Electrophoretic mobility shift assays (EMSA) to study binding.
• Fluorescence lifetime measurements of thiazole orange.
• Assays to determine resistance to phosphodiesterase (YybT) cleavage.

Main Results:

• Cyclic diguanylic acid (c-di-GMP) forms G-wires with intercalators.
• The fluorescence lifetime of thiazole orange bound to c-di-GMP is longer than when bound to DNA.
• Complex stability depends on cation and intercalator type.
• Complexes show increased resistance to YybT phosphodiesterase degradation.

Conclusions:

• Complexation with small molecules can slow the cleavage of bacterial cyclic dinucleotides.
• This stabilization strategy has potential for diverse applications in nanotechnology and medicine.