Nucleobase-caged peptide nucleic acids: PNA/PNA duplex destabilization and light-triggered PNA/PNA recognition

Area of Science:

• Chemical Biology
• Nucleic Acid Chemistry
• Organic Synthesis

Background:

• Peptide nucleic acids (PNAs) are DNA/RNA mimics with unique binding properties.
• Controlling PNA hybridization is crucial for applications in diagnostics and therapeutics.
• Masking nucleobases can modulate PNA duplex stability and recognition.

Purpose of the Study:

• To synthesize and incorporate novel caged nucleobases into PNA sequences.
• To investigate the effect of these caged nucleobases on PNA duplex formation.
• To demonstrate the UV-triggered deprotection and restoration of PNA recognition.

Main Methods:

• Synthesis of Fmoc-protected adeninyl and cytosinyl nucleo amino acid building blocks with 2-(o-nitrophenyl)-propyl (NPP) caging groups.
• Incorporation of caged nucleobases into PNA sequences using Fmoc solid-phase synthesis.
• UV-LED irradiation (365 nm) for photolabile protecting group removal.

Main Results:

• The NPP caging group is stable under standard PNA synthesis conditions.
• Caged nucleobases sterically hinder Watson-Crick base pairing, suppressing PNA duplex formation.
• UV irradiation efficiently removes the NPP groups, restoring complementary PNA/PNA recognition.

Conclusions:

• The NPP group serves as an effective photolabile protecting group for adenine and cytosine in aeg-PNA.
• Nucleobase caging allows for tunable control over PNA hybridization.
• UV-triggered deprotection offers a method for reversible control of PNA recognition.