Alpha-homo-DNA and RNA form a parallel oriented non-A, non-B-type double helical structure.

Area of Science:

• Biochemistry
• Molecular Biology
• Origins of Life Research

Background:

• Nucleic acid interactions are crucial for genetic information transfer.
• Previous studies indicated no base pairing between pyranose and furanose nucleic acids, excluding pyranose forms as RNA/DNA precursors.
• The synthesis of alpha-homo-DNA involves base conversion, with N6-benzoyl-5-methylcytosine converting to thymine.

Purpose of the Study:

• To investigate the hybridization potential between alpha-pyranose oligonucleotides (alpha-homo-DNA) and RNA.
• To characterize the structural and biophysical properties of the resulting alpha-homo-DNA:RNA duplex.
• To explore the implications for the evolution of nucleic acids.

Main Methods:

• Synthesis of alpha-homo-DNA oligonucleotides.
• Hybridization experiments with RNA.
• Structural analysis using Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopy.
• Molecular modeling studies.

Main Results:

• Alpha-homo-DNA successfully hybridizes with RNA, forming parallel-oriented duplexes.
• The alpha-homo-DNA:RNA duplex exhibits unique structural features, differing from canonical A- and B-DNA forms, with 15 base pairs per helical turn.
• NMR data reveals specific base orientations (equatorial for alpha-homo-DNA, pseudoaxial for RNA) and larger interstrand distances.
• Hybrids between alpha-homo-DNA and DNA are less stable.

Conclusions:

• Alpha-homo-DNA:RNA represents the first observed hybridization system between pyranose and furanose nucleic acids.
• This finding challenges the general rule that orthogonal base pair orientation prevents hybridization.
• The study provides novel insights into alternative nucleic acid structures and their potential roles in early genetic systems.