Structural insights into G-quadruplexes: towards new anticancer drugs.
DNA G-quadruplexes are DNA secondary structures formed in specific G-rich sequences. DNA sequences that can form G-quadruplexes have been found in regions with biological significance, such as human telomeres and oncogene-promoter regions. DNA G-quadruplexes have recently emerged as a new class of novel molecular targets for anticancer drugs. Recent progress on structural studies of the biologically relevant G-quadruplexes formed in human telomeres and in the promoter regions of human oncogenes will be discussed, as well as recent advances in the design and development of G-quadruplex-interactive drugs. DNA G-quadruplexes can readily form in solution under physiological conditions and are globularly folded nucleic acid structures. The molecular structures of intramolecular G-quadruplexes appear to differ from one another and, therefore, in principle may be differentially regulated and targeted by different proteins and drugs.
Yang
Danzhou
D
College of Pharmacy, The University of Arizona, 1703 E. Mabel St., Tucson, AZ 85721, USA. yang@pharmacy.arizona.edu
Okamoto
Keika
K
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D054856:G-Quadruplexes; D016259:Genes, myc; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009857:Oncogenes; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D016615:Telomere / Q000235:genetics
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004247:DNA