G-quadruplex binding ligands: from naturally occurring to rationally designed molecules.

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Guanine-rich sequences form G-quadruplex structures (four-stranded DNA/RNA) stabilized by Hoogsteen hydrogen bonds.
• G-quadruplexes play roles in regulating gene expression at transcriptional and translational levels.
• These structures represent promising therapeutic targets for developing novel anticancer drugs.

Purpose of the Study:

• To provide a concise, current overview of ligands that bind to G-quadruplex structures.
• To discuss the structural features of these ligands and their interaction mechanisms with G-quadruplexes.
• To inform the rational design of selective DNA or RNA G-quadruplex targeting agents.

Main Methods:

• Literature review of G-quadruplex binding ligands.
• Categorization of ligands into natural products, synthetic compounds, and computationally identified molecules.
• Analysis of key structural motifs (aromatic core, basic side chains) and their binding interactions.

Main Results:

• Summary of diverse G-quadruplex binding ligands, including natural, synthetic, and computationally screened compounds.
• Identification of common structural motifs in ligands, such as aromatic cores and basic side chains.
• Elucidation of ligand-G-quadruplex interaction principles.

Conclusions:

• Understanding ligand-G-quadruplex interactions is key for drug development.
• Rational design strategies can enhance selectivity for DNA or RNA G-quadruplexes.
• G-quadruplex ligands hold significant potential in anticancer therapeutics.