Novel nucleic acids with left-handed helicity

Area of Science:

• Biochemistry
• Molecular Biology
• Synthetic Chemistry

Background:

• Oligonucleotides are crucial in biological processes and therapeutics.
• Understanding modified nucleic acid structures is key to advancing molecular biology.
• Homo-N-oligonucleotides represent a novel class of synthetic nucleic acid analogs.

Purpose of the Study:

• To synthesize and characterize homo-N-oligonucleotides.
• To investigate the structural properties and pairing capabilities of these novel oligonucleotides.
• To explore their potential as building blocks for new nucleic acid structures.

Main Methods:

• Synthesis of oligonucleotides with a methylene bridge (homo-N-oligonucleotides).
• Thermal denaturation (melting curves) to assess duplex stability and cross-pairing.
• Circular dichroism (CD) spectroscopy to determine secondary structure.
• Nuclear Magnetic Resonance (NMR) spectroscopy (NOESY) for structural confirmation.
• Atomic Force Microscopy (AFM) for visualizing helical conformation.

Main Results:

• Homo-N-oligonucleotides were successfully synthesized.
• Melting curves confirmed cross-pairing ability with both homo-type and natural oligonucleotides.
• CD spectra indicated a left-handed stacked conformation for homo-type dimers and single/double strands.
• Duplexes formed with natural nucleic acids adopted right-handed helices.
• NMR and AFM provided supporting evidence for the left-handed helical structure of homo-type DNA.

Conclusions:

• Homo-N-oligonucleotides possess unique structural characteristics, including a propensity for left-handed helical conformations.
• These synthetic oligonucleotides demonstrate versatile pairing capabilities with natural nucleic acids.
• The findings open avenues for designing novel nucleic acid-based materials and therapeutics with distinct structural properties.