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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
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Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism
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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
PubMed
Summary

Conformationally Restricted Nucleotides (CRNs) are 2

Keywords:
Bridged nucleic acidsantisense oligonucleotidesbinding affinitylocked nucleic acidsthermodynamic stability

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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.