Triplex-forming peptide nucleic acids as emerging ligands to modulate structure and function of complex RNAs

Area of Science:

• Molecular Biology
• Biochemistry
• Synthetic Chemistry

Background:

• RNA's role has evolved from protein synthesis to a major biological regulator.
• Peptide nucleic acids (PNAs) are emerging as potent ligands for RNA recognition.
• PNAs exhibit high sequence specificity and affinity for RNA, surpassing small molecule ligands.

Purpose of the Study:

• To review the potential of PNAs as research tools and therapeutic agents targeting RNA.
• To discuss challenges in PNA applications, including sequence limitations, cellular uptake, and off-target effects.
• To highlight recent advancements in synthetic nucleic acid chemistry addressing these challenges.

Main Methods:

• Review of emerging studies on PNA-RNA interactions.
• Analysis of PNA's triple-helical binding capabilities.
• Discussion of synthetic chemistry approaches to improve PNA efficacy and delivery.

Main Results:

• PNAs demonstrate high sequence specificity and affinity for RNA, enabling triple-helical binding.
• PNA binding can modulate RNA biological functions and conformational dynamics.
• Synthetic chemistry is providing solutions for PNA sequence recognition, delivery, and specificity.

Conclusions:

• PNAs hold significant potential as research tools and therapeutic compounds for RNA targeting.
• Overcoming limitations in sequence recognition, cellular uptake, and bioavailability is crucial for PNA advancement.
• Innovative synthetic nucleic acid chemistry is key to unlocking the full therapeutic and research potential of PNAs.