Ribonucleic guanidine demonstrates an unexpected marked preference for complementary DNA rather than RNA

Area of Science:

• Biochemistry
• Molecular Biology
• Oligonucleotide Chemistry

Background:

• DNA and RNA are nucleic acids with phosphodiester backbones.
• Guanidinium linkages can replace phosphodiester bonds, forming DNG and RNG.
• Oligonucleotides are investigated for therapeutic applications like antigene agents.

Purpose of the Study:

• To evaluate the stability of mixed duplexes involving DNG and RNG.
• To understand the structural basis for the stability differences between RNG-DNA and RNG-RNA hybrids.
• To assess the potential of RNG oligomers as antigene agents.

Main Methods:

• Synthesis of DNG and RNG oligomers.
• Formation and analysis of mixed duplexes (e.g., RNG-U5.DNA-A5).
• Thermodynamic stability measurements (e.g., melting temperature analysis).
• Structural analysis to determine duplex conformation.

Main Results:

• A stability order for mixed duplexes was established: RNG-U5.DNA-A5>>RNA-U5.RNA-A5>RNG-U5.RNA-A5>RNA-U5.DNA-A5>DNA-T5.DNA-A5.
• RNG.DNA duplexes exhibit significantly higher stability than RNG.RNA duplexes.
• The rigidity of the RNG backbone, favoring B-form, contributes to its lower affinity for A-form RNA.

Conclusions:

• RNG oligomers demonstrate preferential binding to DNA over RNA.
• The structural properties of RNG contribute to its selective binding.
• RNG-based molecules are promising candidates for DNA-specific antigene therapies with reduced off-target binding to non-coding RNA (ncRNA).