Stable triplex formation using the strong stacking effect of consecutive thionucleoside moieties

Area of Science:

• Biochemistry
• Organic Chemistry
• Molecular Biology

Background:

• DNA triplexes are crucial for various biological processes.
• Understanding factors that stabilize DNA triplexes is important for therapeutic applications.
• Protonation of DNA bases affects their structure and function.

Purpose of the Study:

• To investigate the effect of thiocarbonyl groups on DNA triplex stability.
• To determine how modified nucleobases influence the pKa of cytosine derivatives in triplexes.

Main Methods:

• Synthesis of modified nucleobases containing thiocarbonyl groups (s(2)T and m(5)s(2)C).
• Formation and characterization of DNA triplexes incorporating these modified bases.
• Spectroscopic analysis to assess triplex stability and pKa values.

Main Results:

• The arrangement of consecutive thiocarbonyl groups in s(2)T and m(5)s(2)C significantly stabilized the pre-protonated form of the DNA triplex.
• This stabilization led to an observable increase in the pKa value of a cytosine derivative within the triplex structure.

Conclusions:

• Thiocarbonyl modifications can be strategically employed to enhance DNA triplex stability.
• The observed pKa shift suggests altered base-pairing and protonation dynamics in modified triplexes.
• These findings have implications for the design of novel nucleic acid-based therapeutics and diagnostics.