Beyond small molecules: targeting G-quadruplex structures with oligonucleotides and their analogues

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• G-quadruplexes (G4s) are vital secondary structures in G-rich DNA/RNA sequences.
• Their locations in critical genomic regions like proto-oncogenes and telomeres impact gene regulation.
• While small molecule stabilizers are numerous, sequence-specific G4 targeting probes are less developed.

Purpose of the Study:

• To review and analyze oligonucleotide-based strategies for G-quadruplex recognition and targeting.
• To highlight the potential of synthetic analogues like LNAs and PNAs in G4-specific applications.
• To provide a critical overview of current literature on G4-targeting probes.

Main Methods:

• Literature review of G-quadruplex targeting strategies.
• Analysis of oligonucleotide-based probes, including Locked Nucleic Acids (LNAs) and Peptide Nucleic Acids (PNAs).
• Critical evaluation of reported examples and their effectiveness in sequence-specific G4 recognition.

Main Results:

• Oligonucleotide-based probes offer a promising avenue for sequence-specific G4 targeting.
• LNAs and PNAs demonstrate potential as effective G4 recognition and binding agents.
• The field of synthetic probe-based G4 targeting is still evolving with room for advancement.

Conclusions:

• Oligonucleotide and synthetic analogues represent a key strategy for targeted G4 modulation.
• Further research into these probes can unlock new therapeutic and diagnostic applications for G4 structures.
• This review consolidates current knowledge and identifies future directions for G4-targeting probe development.