title: A Selective G-Quadruplex DNA-Stabilizing Ligand Based on a Cyclic Naphthalene Diimide Derivative.
abstract: A cyclic naphthalene diimide (cyclic NDI, 1), carrying a benzene moiety as linker chain, was synthesized and its interaction with G-quadruplex DNAs of a-core and a-coreTT as a human telomeric DNA, c-kit and c-myc as DNA sequence at promoter region, or thrombin-binding aptamer (TBA) studied based on UV-VIS and circular dichroism (CD) spectroscopic techniques, thermal melting temperature measurement, and FRET-melting assay. The circular dichroism spectra showed that 1 induced the formation of different types of G-quadruplex DNA structure. Compound 1 bound to these G-quadruplexes with affinities in the range of 106-107 M-1 order and a 2:1 stoichiometry. Compound 1 showed 270-fold higher selectivity for a-core than dsDNA with a preferable a-core binding than a-coreTT, c-kit, c-myc and TBA in the presence of K+, which is supported by thermal melting studies. The FRET-melting assay also showed that 1 bound preferentially to human telomeric DNA. Compound 1 showed potent inhibition against telomerase activity with an IC50 value of 0.9 μM and preferable binding to G-quadruplexes DNA than our previously published cyclic NDI derivative 3 carrying a benzene moiety as longer linker chain.
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan. monirbtge@takenaka.che.kyutech.ac.jp.
authors.forename: Md Monirul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan. s.fujii@bio.kyutech.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan. shinobu@che.kyutech.ac.jp.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan. okauchi@che.kyutech.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Okauchi
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan. shige@che.kyutech.ac.jp.
authors.forename: Shigeori
authors.initials: S
authors.lastname: Takenaka
mesh_terms: D002942:Circular Dichroism; D054856:G-Quadruplexes / Q000187:drug effects*; D007094:Imides / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D044366:Transition Temperature
chemical_list: D007094:Imides; D008024:Ligands; D009281:Naphthalenes; C542131:naphthalenediimide
keywords: G-quartet; cyclic naphthalene diimide; human telomeric DNA; promoter region; thrombin-binding aptamer