G‐Quadruplex Structures and Their Interaction Diversity with Ligands

Abstract

G‐Quadruplexes are distinct nucleic acid secondary structures that are formed from G‐rich DNA and RNA sequences; they are built around successive G‐tetrads of Hoogsteen hydrogen‐bonded guanine bases. The existence of G‐quadruplex structures has been confirmed in the human telomere and genome, and their biological functions have been demonstrated. Thus, the prospect of using G‐quadruplex structures as a novel target for drug design is important. This review focuses on structural polymorphism of G‐quadruplexes on the basis of the classification of the strand number of the G‐quadruplex formed and its interaction diversity with small molecules (G4‐ligands) that display high affinity and, more importantly, selectivity. Also, we outlook some future challenges for G‐quadruplex structure and ligand studies. Such information, together with the biological functions of for G‐quadruplex, will be of crucial importance for the research and development of drugs that target G‐quadruplexes formed from particular genes and human telomeres.