G4-interacting ligands: paving the way for precision medicine and molecular diagnostics.

Amidst the ever-evolving landscape of biomedical research, G-quadruplex (G4) structures have emerged as captivating therapeutic targets, holding immense promise for precision medicine and molecular diagnostics. These intricate DNA or RNA formations play crucial roles in regulating gene expression and are implicated in the pathogenesis of various diseases, including cancer and neurological disorders. The interaction between G4s and ligands derived from medicinal plants offers a compelling avenue for therapeutic intervention and diagnostic applications. G4-interacting ligands have demonstrated remarkable potential as therapeutic agents, selectively targeting G4 structures and modulating their biological functions. However, the effective delivery of these ligands into living cells remains a formidable challenge. Existing physical and biochemical methods are often limited to in vitro settings due to concerns regarding toxicity and nonspecific binding. Overcoming this delivery hurdle is paramount for translating G4-targeting therapies into clinically viable treatments. The development of novel G4 ligands with enhanced affinity and selectivity is essential for realizing the full therapeutic potential of G4-targeting strategies. Understanding the shared structural features of G4 ligands, such as the presence of an aromatic core for π-π stacking interactions and positive moieties for interactions with DNA or RNA backbones, provides valuable insights into ligand design. G4/ligand interactions hold immense promise for molecular diagnostics. By exploiting the specific recognition and binding capabilities of G4 ligands, researchers can develop biosensors and bioimaging tools for the detection and diagnosis of G4-related diseases. These diagnostic tools have the potential to revolutionize disease management by enabling early detection, personalized treatment plans, and improved patient outcomes.Communicated by Ramaswamy H. Sarma.