New nucleotide pairs for stable DNA triplexes stabilized by stacking interaction

Area of Science:

• Biochemistry
• Molecular Biology
• Synthetic Chemistry

Background:

• DNA triplexes are crucial for gene regulation and DNA nanotechnology.
• Developing novel nucleotide analogs is key to expanding triplex stability and sequence diversity.

Purpose of the Study:

• To design and synthesize novel nucleotide analogs for DNA triplex formation.
• To investigate the impact of modified nucleobases on triplex stability and recognition.

Main Methods:

• Synthesis of 5-aryl deoxycytidine derivatives (dC5Ars) and cyclic deoxycytidine derivatives (dCPPP, dCPPI).
• Incorporation of these modified nucleotides into oligonucleotides for the second strand of DNA triplexes.
• Utilizing abasic residues (C3 and phi) as pairing partners.

Main Results:

• The incorporation of dC5Ars and cyclic deoxycytidine derivatives into DNA triplexes was successful.
• A significant increase in triplex stability was observed when 5-aryl-modified cytosine bases paired with abasic sites in a space-fitting manner.
• Selective recognition of C3 by dC5Ars was attributed to favorable stacking interactions with flanking nucleobases.

Conclusions:

• Novel nucleotide triplets can be formed, expanding the structural and sequence diversity of DNA triplexes.
• These modified nucleotides show potential for applications in biorelated fields, particularly DNA nanotechnologies.
• The findings provide a foundation for designing more stable and versatile DNA triplex structures.