title: Recent developments in the chemistry and biology of G-quadruplexes with reference to the DNA groove binders.
abstract: DNA is the chemotherapeutic target for treating diseases of genetic origin. Besides well-known double-helical structures (A, B, Z, parallel stranded-DNA etc.), DNA is capable of forming several multi-stranded structures (triplex, tetraplex, i-motif etc.) which have unique biological significance. The G-rich 3'-ends of chromosomes, called telomeres, are synthesized by telomerase, a ribonucleoprotein, and over-expression of telomerase is associated with cancer. The activity of telomerase is suppressed if the G-rich region is folded into the four stranded structures, called G-quadruplexes (G4-DNAs) using small synthetic ligands. Thus design and synthesis of new G4- DNA ligands is an attractive strategy to combat cancer. G4-DNA forming sequences are also prevalent in other genomic regions of biological significance including promoter regions of several oncogenes. Effective gene regulation may be achieved by inducing a G4-DNA structure within the G-rich promoter sequences. To date, several G4-DNA stabilizing ligands are known. DNA groove binders interact with the duplex B-DNA through the grooves (major and minor groove) in a sequence-specific manner. Some of the groove binders are known to stabilize the G4-DNA. However, this is a relatively under explored field of research. In this review, we focus on the recent advances in the understanding of the G4-DNA structures, particularly made from the human telomeric DNA stretches. We summarize the results of various investigations of the interaction of various organic ligands with the G4-DNA while highlighting the importance of groove binder-G4-DNA interactions.
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore, India.
authors.forename: Akash K
authors.initials: AK
authors.lastname: Jain
authors.forename: Santanu
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D016615:Telomere
chemical_list: D008024:Ligands; D004247:DNA