Highly polar carbohydrates stack onto DNA duplexes via CH/π interactions

Area of Science:

• Biochemistry
• Chemical Biology
• Materials Science

Background:

• Carbohydrate-nucleic acid interactions are crucial in drug-DNA recognition, primarily via DNA grooves.
• Existing interactions involve minor groove binders (e.g., calicheamicin) or dual groove binders (e.g., pluramycins).

Purpose of the Study:

• To investigate novel carbohydrate-DNA interaction modes beyond groove binding.
• To explore the potential of sugar capping as a DNA recognition mechanism.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study interactions.
• Analysis of CH/π stacking between mono- and disaccharides and terminal DNA base pairs.

Main Results:

• Mono- and disaccharides can form CH/π stacks with the terminal base pair of DNA duplexes.
• Interaction energetics are influenced by sugar stereochemistry, polarity, and DNA terminal base pair composition.
• Demonstrated carbohydrate-DNA base stacking as a viable interaction motif.

Conclusions:

• Carbohydrate-DNA base stacking represents a new mode of molecular recognition.
• This interaction offers potential applications in drug design, supramolecular chemistry, and biobased nanomaterials.