G-Quadruplexes: Targets in Anticancer Drug Design

G‐quadruplexes are special secondary structures adopted in some guanine‐rich DNA sequences. As guanine‐rich sequences are present in important regions of the eukaryotic genome, such as telomeres and the regulatory regions of many genes, such structures may play important roles in the regulation of biological events in the body. G‐quadruplexes have become valid targets for new anticancer drugs in the past few decades. Many leading compounds that target these structures have been reported, and a few of them have entered preclinical or clinical trials. Nonetheless, the selectivity of this kind of antitumor compound has yet to be improved in order to suppress the side effects caused by nonselective binding. As drug design targets, the topology and structural characteristics of quadruplexes, their possible biological roles, and the modes and sites of small‐ligand binding to these structures should be understood clearly. Herein we provide a summary of published research that has set out to address the above problem to provide useful information on the design of small ligands that target G‐quadruplexes. This review also covers research methodologies that have been developed to study the binding of ligands to G‐quadruplexes. Important regions in the human genome such as telomeres and oncogene promoters have the potential to fold into G‐quadruplexes. The formation or stabilization of these structures by G‐quadruplex ligands may influence the biological function of the given gene or telomere, and thus have some effect on disease control. The study of such ligands has involved genomic, biochemical, biophysical, and molecular biological methods.