G-Quadruplex conformational change driven by pH variation with potential application as a nanoswitch.

Area of Science:

• Structural biology
• Supramolecular chemistry
• Nanotechnology

Background:

• G-quadruplex structures are highly polymorphic.
• Their behavior under acidic conditions remains largely unexplored.

Purpose of the Study:

• To investigate the conformational changes of G-quadruplex structures in acidic conditions.
• To identify G-quadruplex sequences with significant pH-responsive transformations.
• To explore the potential of these transformations in designing DNA-based nanodevices.

Main Methods:

• Circular dichroism (CD) spectroscopy to monitor conformational changes and thermal stability.
• CD kinetics to study interconversion rates.
• 2-Aminopurine (Ap) fluorescence to assess loop dynamics.
• Proton Nuclear Magnetic Resonance (NMR) for structural elucidation.

Main Results:

• Specific G-quadruplex sequences exhibit pH-dependent conformational transformations.
• Loop rearrangement is the primary mechanism driving these pH-induced changes.
• A G-quadruplex sequence with a TT central loop showed superior transformation properties under milder conditions compared to a TTA loop.
• A pH-driven nanoswitch utilizing this transition was successfully designed.

Conclusions:

• G-quadruplex structures can undergo significant conformational changes at low pH.
• The DNA loop sequence critically controls pH-responsive interconversion.
• These findings advance the understanding of G-quadruplex polymorphism and facilitate the design of DNA nanomachines and logic gates.