Minor groove tetrads: a potent and versatile capping interaction for i-motif structures

Area of Science:

• Structural biology
• DNA nanotechnology
• Biochemistry

Background:

• i-Motif DNA structures are G-quadruplex analogs with potential in nanotechnology.
• Their stability and folding are often pH-dependent, limiting applications.
• Minor groove tetrads (MGTs) are non-canonical base pairings that can stabilize DNA structures.

Purpose of the Study:

• To investigate the role of MGTs in enhancing the stability and versatility of i-motif DNA structures.
• To explore the structural properties and potential applications of MGT-containing i-motifs (MGTiMs).
• To provide principles for rational i-motif engineering using MGT stabilization.

Main Methods:

• Formation and characterization of MGT-containing i-motifs (MGTiMs).
• Analysis of MGTiM structural properties, including thermal and pH stability.
• Investigation of MGTiM integration into DNA duplex junctions and response to chemical modifications.

Main Results:

• MGTs reinforce hemiprotonated C:C+ stacks, enabling i-motif folding at neutral pH.
• MGTiMs exhibit exceptional thermal and pH stability, tunable topology, and structural plasticity.
• MGTiMs can form compact architectures, undergo reversible pH-dependent transitions, and integrate into B-DNA without distortion.

Conclusions:

• MGTs provide a powerful strategy for engineering stable, predictable, and responsive i-motif DNA nanostructures.
• The synergy of MGT stabilization with chemical modifications enables advanced applications like real-time monitoring and in-cell imaging.
• MGTiMs hold significant potential for biosensing, nanotechnology, and synthetic biology applications.