Oligodeoxynucleotides containing alpha-L-ribo configured LNA-type C-aryl nucleotides

Area of Science:

• Organic Chemistry
• Nucleoside Chemistry
• Biochemistry

Background:

• Locked nucleic acids (LNA) are modified nucleic acids with enhanced binding affinity and stability.
• C-aryl nucleosides offer unique structural and functional properties for oligonucleotide applications.

Purpose of the Study:

• To synthesize novel alpha-L-ribo configured LNA-type C-aryl nucleosides containing phenyl and 1-pyrenyl aglycons.
• To incorporate these novel monomers into oligonucleotides for assessing their hybridization properties.

Main Methods:

• Stereoselective Grignard reactions and Mitsunobu cyclization were employed for synthesizing the bicyclic furanosyl skeleton.
• Phosphoramidite derivatives were used for automated synthesis of DNA and LNA oligonucleotides.
• Thermal denaturation studies (UV-Vis spectroscopy) were conducted to evaluate base pairing behavior.

Main Results:

• Novel alpha-L-ribo configured LNA-type C-aryl nucleosides with phenyl and pyrenyl aglycons were successfully synthesized.
• Automated synthesis yielded 9-mer DNA and LNA oligonucleotides containing these novel monomers.
• The pyrenyl-containing monomer demonstrated universal base pairing properties when incorporated into DNA or LNA strands.

Conclusions:

• The developed synthetic route provides access to unique LNA-type C-aryl nucleosides.
• Incorporation of these monomers into oligonucleotides is feasible via automated synthesis.
• The pyrenyl monomer exhibits promising universal base pairing, suggesting potential applications in nucleic acid therapeutics and diagnostics.