title: A novel transition pathway of ligand-induced topological conversion from hybrid forms to parallel forms of human telomeric G-quadruplexes.
abstract: The folding topology of DNA G-quadruplexes (G4s) depends not only on their nucleotide sequences but also on environmental factors and/or ligand binding. Here, a G4 ligand, 3,6-bis(1-methyl-4-vinylpyridium iodide)-9-(1-(1-methyl-piperidinium iodide)-3,6,9-trioxaundecane) carbazole (BMVC-8C3O), can induce topological conversion of non-parallel to parallel forms in human telomeric DNA G4s. Nuclear magnetic resonance (NMR) spectroscopy with hydrogen-deuterium exchange (HDX) reveals the presence of persistent imino proton signals corresponding to the central G-quartet during topological conversion of Tel23 and Tel25 G4s from hybrid to parallel forms, implying that the transition pathway mainly involves local rearrangements. In contrast, rapid HDX was observed during the transition of 22-CTA G4 from an anti-parallel form to a parallel form, resulting in complete disappearance of all the imino proton signals, suggesting the involvement of substantial unfolding events associated with the topological transition. Site-specific imino proton NMR assignments of Tel23 G4 enable determination of the interconversion rates of individual guanine bases and detection of the presence of intermediate states. Since the rate of ligand binding is much higher than the rate of ligand-induced topological conversion, a three-state kinetic model was evoked to establish the associated energy diagram for the topological conversion of Tel23 G4 induced by BMVC-8C3O.
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan, Republic of China.
authors.forename: Zi-Fu
authors.initials: ZF
authors.lastname: Wang
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan, Republic of China.
authors.forename: Ming-Hao
authors.initials: MH
authors.lastname: Li
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan, Republic of China Molecular Science and Technology Program, Taiwan International Graduate Program, Academia Sinica, Taipei 106, Taiwan, Republic of China Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Chen
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan, Republic of China Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, Taiwan, Republic of China sthsu@gate.sinica.edu.tw.
authors.forename: Shang-Te Danny
authors.initials: ST
authors.lastname: Hsu
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan, Republic of China tcchang@po.iams.sinica.edu.tw.
authors.forename: Ta-Chau
authors.initials: TC
authors.lastname: Chang
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D002227:Carbazoles / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D007700:Kinetics; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D016615:Telomere / Q000737:chemistry*
chemical_list: D000097:Acetonitriles; C000619772:BMVC-8C3O; D002227:Carbazoles; D008024:Ligands; D004247:DNA; C032159:acetonitrile