Convertible and conformationally constrained nucleic acids (C₂NAs)

Area of Science:

• Chemical Biology
• Nucleic Acid Chemistry
• Biotechnology

Background:

• DNA structural flexibility is crucial for biological function.
• Controlling DNA conformation is key for therapeutic and diagnostic applications.
• Existing nucleic acid modifications have limitations in versatility and stability.

Purpose of the Study:

• To introduce a novel class of nucleic acids, Convertible and Constrained Nucleic Acids (C2NAs).
• To demonstrate the ability of C2NAs to modulate DNA structural properties.
• To enable facile functionalization of nucleic acids using click chemistry.

Main Methods:

• Synthesis of a stereocontrolled N-propargyl dioxo-1,3,2-oxaza-phosphorinane internucleotidic linkage.
• Utilizing the linkage to control torsional angles (α and β) in nucleic acids.
• Employing copper-catalyzed Huisgen's cycloaddition (CuAAC click chemistry) for functionalization.

Main Results:

• C2NAs can adopt canonical (g-, t) or non-canonical (g+, t) torsional angles.
• The (g-, t) conformation enhances DNA duplex stability.
• The (g+, t) conformation stabilizes hairpin structures within nucleic acid loops.
• Click chemistry allows for site-specific introduction of diverse functionalities.

Conclusions:

• C2NAs offer unprecedented control over nucleic acid conformation and stability.
• The developed linkage provides a versatile platform for nucleic acid engineering.
• C2NAs hold promise for applications in DNA-based technologies and therapeutics.