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

Miguel Garavís1, Bartomeu Mir1,2,3,4, Israel Serrano-Chacón1,5

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Biophysical Reviews
|March 30, 2026
PubMed
Summary

Minor groove tetrads (MGTs) stabilize i-motif DNA structures, enabling folding at neutral pH. These MGT-containing i-motifs (MGTiMs) offer enhanced stability and versatility for DNA nanotechnology.

Keywords:
Four-stranded structuresI-MotifNMRNon-canonical nucleic acidsTetrads

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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.