Membrane-Penetrating Molecular Device Based on a Triplex Containing Acyclic L-Threoninol Nucleic Acid Functionalized...

Area of Science:

• Biochemistry
• Molecular Biology
• Nanotechnology

Background:

• Membrane-penetrating molecular devices are crucial for biological research and therapeutic applications.
• Acyclic nucleic acids (aXNAs) offer unique structural and functional properties compared to traditional DNA/RNA.
• Cholesterol conjugation is a common strategy to enhance membrane interaction of nucleic acid-based structures.

Purpose of the Study:

• To design and synthesize novel membrane-targeting molecular devices utilizing acyclic L-threoninol nucleic acid (L-aTNA).
• To investigate the influence of cholesterol linkage orientation on the membrane-binding and penetration capabilities of L-aTNA triplexes.
• To explore the potential of photoresponsive L-aTNA triplexes for signal transduction across membranes.

Main Methods:

• Synthesis of L-aTNA-cholesterol conjugates with specific linkage orientations.
• Characterization of molecular device structure and self-assembly into triplexes with poly A DNA.
• Assessment of membrane interaction using giant unilamellar vesicles (GUVs) to evaluate adhesion and penetration.
• Incorporation of photoresponsive DNA for studying light-induced signal transduction.

Main Results:

• Two distinct membrane-binding behaviors were observed based on cholesterol linkage orientation: adhesion and penetration.
• The L-aTNA triplexes demonstrated efficient membrane penetration.
• Photoresponsive L-aTNA triplexes enabled light-triggered signal transduction into GUVs.
• Post-modification of the propargyl-L-aTNA unit allows for further functionalization.

Conclusions:

• Novel membrane-targeting molecular devices based on L-aTNA-cholesterol conjugates were successfully developed.
• The orientation of cholesterol linkage critically controls membrane interaction, enabling selective adhesion or penetration.
• These devices hold significant promise for applications in biosensing, artificial organs, molecular robotics, and chemical artificial intelligence.
• The presented strategy facilitates versatile functionalization of L-aTNA and other aXNAs for advanced molecular applications.