Not all 2',4'-bridged modifications stabilize DNA/RNA duplexes.
Tomoka Akita1,2, Elisa Tomita-Sudo2, Shin Itoh1
1Faculty of Frontiers of Innovative Research in Science and Technology, Konan University, Kobe, Japan.
Nucleosides, Nucleotides & Nucleic Acids
|July 10, 2023
Summary
Conformationally Restricted Nucleotides (CRNs) are 2
Area of Science:
- Nucleic acid chemistry
- Biochemistry
- Molecular biology
Background:
- 2',4'-bridged nucleic acids, including LNAs and ENAs, enhance DNA/RNA duplex binding affinity.
- This stabilization is attributed to pre-organization of the nucleotide structure.
Purpose of the Study:
- To investigate the effect of 2',4'-C-bridged 2'-deoxynucleotides (CRNs) on DNA/RNA duplex stability.
- To challenge the prevailing assumption that all 2',4'-bridged modifications stabilize nucleic acid duplexes.
Main Methods:
- Synthesis of CRNs.
- Incorporation of CRNs into DNA/RNA duplexes.
- Thermodynamic analysis of duplex stability.
Main Results:
- Introduction of CRNs into DNA/RNA duplexes resulted in destabilization.
- This finding contradicts the established notion of stabilization by 2',4'-bridged modifications.
Conclusions:
- CRNs can destabilize DNA/RNA duplexes, contrary to expectations for 2',4'-bridged nucleic acids.
- The pre-organization model may not universally apply to all bridged nucleotide modifications.
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