Pseudorotaxane formation via the slippage process with chemically cyclized oligonucleotides

Area of Science:

• Molecular Biology
• Supramolecular Chemistry
• Biochemistry

Background:

• Circular nucleic acids offer unique structural properties for diverse applications.
• Chemically-cyclized oligonucleotides (cyODNs) with double-tailed parts can form pseudorotaxanes with targets via slippage.

Purpose of the Study:

• Investigate the slippage properties and mechanism of cyODN-target interactions.
• Characterize the factors influencing pseudorotaxane formation efficiency.
• Explore unique properties of the resulting pseudorotaxanes.

Main Methods:

• Synthesis and utilization of six different cyODNs.
• Systematic investigation of reaction conditions (temperature, ring size, target length, mismatch position).
• Kinetic studies to elucidate the threading mechanism.

Main Results:

• Pseudorotaxane formation efficiency is significantly influenced by temperature, ring size, target length, and mismatch position.
• The formation mechanism involves a non-threaded intermediate that hybridizes with the target at the double-tailed parts.
• Resulting pseudorotaxanes exhibit unique characteristics, including hysteresis loops in Tm measurements and kinetic stabilization.

Conclusions:

• The study elucidates the mechanism of pseudorotaxane formation by cyODNs.
• Findings highlight the importance of reaction parameters for controlling formation efficiency.
• The unique properties of these pseudorotaxanes open avenues for novel applications of circular nucleic acids and understanding molecular threading.