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.

Keywords: G-Quadruplexes; drug design; interaction diversity; ligand effects; polymorphism.