Peptide nucleic acids with a structurally biased backbone. Updated review and emerging challenges

Area of Science:

• Medicinal Chemistry
• Oligonucleotide Analogues
• Molecular Biology

Background:

• Peptide nucleic acids (PNAs) are versatile oligonucleotide analogues with strong DNA/RNA binding capabilities.
• PNAs have shown promise in diagnostics, gene regulation, and as potential therapeutic agents.
• Advancements in delivery systems and anti-gene strategies are enhancing PNA therapeutic applications.

Purpose of the Study:

• To review modifications of the PNA backbone.
• To explore the medicinal chemistry applications of these modified PNAs.
• To highlight emerging trends and new possibilities in PNA research.

Main Methods:

• Focus on structurally biased PNAs, specifically acyclic and cyclic variants.
• Detailed description of PNA backbone modifications.
• Discussion of PNA properties, including nucleic acid affinity.

Main Results:

• Acyclic PNAs exhibit stereochemistry-regulated helical preference.
• Cyclic PNAs possess preorganized structures with stereochemistry- and conformation-dependent performance.
• Examples of PNA applications in cellular and animal systems are presented.

Conclusions:

• Modified PNAs offer significant potential in medicinal chemistry.
• Structurally biased PNAs, including acyclic and cyclic types, are promising for drug development.
• New research avenues include microRNA targeting and gene repair using PNA technology.