Accelerated assembly of G-quadruplex structures by a small molecule.
In the presence of alkali cations, notably potassium and sodium, DNA oligomers that possess two G-rich repeats associate into either a tetrameric parallel G-quadruplex or a variety of dimeric antiparallel G-quadruplexes. The formation of such structures is normally a very slow process. Some proteins, such as the beta-subunit of the Oxytricha telomere-binding protein, promote the formation of G-quadruplex structures in a chaperone-like manner. In this report, we present data concerning the role of a perylene derivative, PIPER, in the assembly of G-quadruplex structures as the first example of a small ligand behaving as a driver in the assembly of polynucleotide secondary structures. Gel-shift experiments demonstrate that PIPER can dramatically accelerate the association of a DNA oligomer containing two tandem repeats of the human telomeric sequence (TTAGGG) into di- and tetrameric G-quadruplexes. In so doing, PIPER alters the oligomer dimerization kinetics from second to first order. The presence of 10 microM PIPER accelerates the assembly of varied dimeric G-quadruplexes an estimated 100-fold from 2 microM oligomer. These results imply that some biological effects elicited by G-quadruplex-interactive agents, such as the induction of anaphase bridges, may stem from the propensity such compounds have for assembling G-quadruplexes.
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Institute for Cellular and Molecular Biology, Division of Medicinal Chemistry, Drug Dynamics Institute, The University of Texas at Austin 78712, USA.
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Hurley
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D000873:Anthracenes / Q000737:chemistry; D002414:Cations, Monovalent; D004247:DNA / Q000737:chemistry*; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D046911:Macromolecular Substances; D009690:Nucleic Acid Conformation; D010569:Perylene / Q000031:analogs & derivatives; D010880:Piperidines / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D013463:Sulfuric Acid Esters / Q000737:chemistry; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000235:genetics
D000873:Anthracenes; D002414:Cations, Monovalent; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C116108:N,N'-bis(2-1(piperidino)-ethyl)-3,4,9,10-perylene-tetracarboxylic diimide; D010880:Piperidines; D013463:Sulfuric Acid Esters; D010569:Perylene; D006147:Guanine; D004247:DNA; C007482:dimethyl sulfate; D011188:Potassium