title: Cyclic ferrocenylnaphthalene diimide derivative as a new class of G-quadruplex DNA binding ligand.
abstract: To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (106M-1order) with diminished binding to dsDNA (104M-1order) in 100mM AcOH-AcOK buffer (pH 5.5) containing 100mM KCl. Interestingly, 1 showed an approximately 50-fold higher selectivity to mixed hybrid-type telomeric G-quadruplex DNA (K=3.4×106M-1and a 2:1 stoichiometry) than dsDNA (K=7.5×104M-1) did. Furthermore, 1 showed higher thermal stability to G-quadruplex DNAs than it did to dsDNA with a preference for c-kit and c-myc G-quadruplex DNAs over telomeric and thrombin binding aptamers. Additionally, 1 exhibited telomerase inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.4μM. Compound 2 showed a preference for G-quadruplex; however, the binding affinity magnitude and preference were improved in 1 because the former had a cyclic structure.
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu 804-8550, Japan.
authors.forename: Md Monirul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu 804-8550, Japan; Center for Bio-microsensing Technology, Kyushu Institute of Technology, Kitakyushu 804-8550, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu 804-8550, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Shinozaki
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu 804-8550, Japan; Center for Bio-microsensing Technology, Kyushu Institute of Technology, Kitakyushu 804-8550, Japan. Electronic address: shige@che.kyutech.ac.jp.
authors.forename: Shigeori
authors.initials: S
authors.lastname: Takenaka
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D007094:Imides; D008024:Ligands; C406363:ferrocenylnaphthalene diimide; D019098:Telomerase
keywords: Cyclic ferrocenylnaphthalene diimide; Double stranded DNA; G-quadruplex DNA; Human telomere DNA; Promotor region; Tetraplex DNA binder; Thrombin binding aptamer