title: Synthesis of a single G-quartet platform in water.
abstract: For over 50 years the G-quartet has been a defining self-assembled structure in biology and non-covalent synthesis. It is shown here for the first time that the G-quartet is isolatable in water in the absence of stabilizing G-quartet stacking or cations through the construction of a phosphate-linked template-assembled synthetic G-quartet. Synthetic design has facilitated preservation of the guanine base, ribose sugar, and phosphate components with correct linkage chemistry relative to G-quadruplex DNA. Thus, a minimal synthetic model of G-quadruplex DNA, as in that associated with human gene promoter or telomere regions, is represented by this system. An application as a probe for interactions between G-quadruplex DNA and potential anticancer therapeutical binding ligands is demonstrated. Binding constants of 10(5)-10(7) M(-1) magnitude and 1:1 stoichiometries for TMPyP4, piper, and azatrux ligands were determined, whereas perturbations in BSU1051 and BRACO19 ligand signal were not observed. These data suggest a unique test for critical end-stacking interactions at the exclusion of intercalative or looping interactions for G-quadruplex binding ligands.
authors.affiliation: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Grant A L
authors.initials: GA
authors.lastname: Bare
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: John C
authors.initials: JC
authors.lastname: Sherman
mesh_terms: D000166:Acridines / Q000494:pharmacology; D000880:Anthraquinones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D014867:Water / Q000737:chemistry
chemical_list: D000166:Acridines; D000880:Anthraquinones; D000970:Antineoplastic Agents; C117697:BSU 1051; D002227:Carbazoles; D008024:Ligands; C116108:N,N'-bis(2-1(piperidino)-ethyl)-3,4,9,10-perylene-tetracarboxylic diimide; D010880:Piperidines; D011166:Porphyrins; C568450:azatrux; D014867:Water; C021096:tetra(4-N-methylpyridyl)porphine; D010569:Perylene; D004247:DNA; C454064:BRACO-19