Sulfonamide bearing oligonucleotides: simple synthesis and efficient RNA recognition

Area of Science:

• Nucleic acid chemistry
• Medicinal chemistry
• Supramolecular chemistry

Background:

• Pyrimidine nucleosides are fundamental building blocks of nucleic acids.
• Modifications to nucleobases can alter oligonucleotide properties.
• Understanding stacking interactions is crucial for nucleic acid stability.

Purpose of the Study:

• To synthesize novel pyrimidine nucleosides with benzensulfonamide groups.
• To investigate the impact of triazolyl and alkynyl linkers on oligonucleotide stability.
• To explore the role of phenyltriazole stacking in DNA:RNA duplexes.

Main Methods:

• Cu(I)-assisted azide-alkyne cycloadditions (CuAAC) for triazole formation.
• Sonogashira reactions for alkynyl linker synthesis.
• Incorporation of modified nucleosides into oligonucleotides.
• Thermal stability assays of DNA:RNA duplexes.

Main Results:

• Phenyltriazole moieties significantly increased DNA:RNA duplex thermal stability via π-π stacking.
• Triazolyl linkers demonstrated superior stacking efficiency compared to alkynyl linkers.
• Optimal stability was observed with four consecutive sulfonamide-substituted phenyltriazole groups in the major groove.
• Positional orientation of the sulfonamide group did not affect stacking efficiency.

Conclusions:

• Benzensulfonamide-functionalized phenyltriazoles are effective in stabilizing DNA:RNA duplexes.
• The observed stabilization is attributed to efficient π-π stacking interactions.
• These findings offer insights into designing modified oligonucleotides with enhanced thermal properties.