Nucleobase azide-ethynylribose click chemistry contributes to stabilizing oligonucleotide duplexes and stem-loop
Yoshiaki Kitamura1, Ryo Asakura2, Koki Terazawa2
1Department of Biomolecular Science, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Bioorganic & Medicinal Chemistry Letters
|May 2, 2017
Summary
Copper-catalyzed azide-alkyne cycloaddition (CuAAC) forms 1,4-disubstituted 1,2,3-triazoles in modified oligonucleotides. This modification enhances the stability of oligonucleotide duplexes and stem-loop structures.
Area of Science:
- Chemical Biology
- Nucleic Acid Chemistry
- Organic Synthesis
Background:
- Oligonucleotides are crucial in various biological processes and therapeutic applications.
- Modifying oligonucleotide structures can improve their stability and functionality.
- Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a versatile click chemistry reaction.
Purpose of the Study:
- To investigate the impact of incorporating 1-deoxy-1-ethynyl-β-d-ribofuranose (R^E) into oligonucleotides.
- To synthesize 1,4-disubstituted 1,2,3-triazoles within oligonucleotide chains using CuAAC.
- To evaluate the effect of these modifications on oligonucleotide structural stability.
Main Methods:
- Oligonucleotide synthesis incorporating R^E phosphoramidites.
- Copper-catalyzed azide-alkyne cycloaddition (CuAAC) for triazole formation.
- Analysis of oligonucleotide duplex and stem-loop stability using biophysical methods.
Main Results:
- Successful synthesis of oligonucleotides containing 1,4-disubstituted 1,2,3-triazoles via CuAAC.
- Demonstrated enhancement in the thermal stability of oligonucleotide duplexes.
- Improved stability of oligonucleotide stem-loop structures observed.
Conclusions:
- The incorporation of 1,4-disubstituted 1,2,3-triazoles through CuAAC in R^E-modified oligonucleotides is feasible.
- These modifications significantly enhance the stability of oligonucleotide secondary structures.
- This strategy offers a promising approach for developing more stable oligonucleotide-based therapeutics and research tools.
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