G-Quadruplex and Ligand Interactions

Designing ligands to interact with G-quadruplex (G4) of DNA is challenging due to the complexity of G4 structures and the lack of efficient experimental methods to characterize G4/ligand interactions. Existing methods can be categorized into structure-based (e.g., CD, NMR, X-ray crystallography), affinity-based (e.g., SPR, ITC, MS), and high-throughput (e.g., FRET, G4-FID, affinity chromatography, microarrays) approaches, each with its own advantages and disadvantages. High-throughput methods are emerging as a promising alternative to traditional methods for screening and designing new G4 ligands, as they are faster and more cost-effective.

G4s are found in both DNA and RNA and play an important role in a variety of physiological processes, including cancer and neurological disorders. Targeting G4s with ligands is a promising therapeutic strategy for these diseases. A significant number of G4 ligands have been developed and investigated, and most of them are deposited in the G4 Ligands Database 2.1 (http://www.g4ldb.com/).