title: Design and synthesis of unsymmetric macrocyclic hexaoxazole compounds with an ability to induce distinct G-quadruplex topologies in telomeric DNA.
abstract: New macrocyclic hexaoxazole compounds bearing two side chains on an unsymmetrical macrocyclic ring system, i.e., 4,2-L2H2-6OTD (2) and 5,1-L2H2-6OTD (3), were designed as candidate G-quadruplex (G4) ligands and synthesized. These G4 ligands 2 and 3 induced an anti-parallel topology and a hybrid-type topology of telomeric DNA, respectively, in contrast to the previously reported symmetrical macrocycle 3,3-L2H2-6OTD (1), which induces a typical anti-parallel structure. Molecular mechanics calculations and docking studies indicate that these differences arise from the different directions of the side chains in these L2H2-6OTD derivatives, and provide an explanation for the weaker stabilization of telomeric DNA by 2 and 3, compared with 1.
authors.affiliation: Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology (TUAT), Koganei, Tokyo 184-8588, Japan. knaga@cc.tuat.ac.jp.
authors.forename: Mai
authors.initials: M
authors.lastname: Sakuma
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Yamato
authors.initials: Y
authors.lastname: Tsushima
authors.forename: Keisuke
authors.initials: K
authors.lastname: Iida
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Hirokawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagasawa
mesh_terms: D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000737:chemistry*; D015195:Drug Design; D054856:G-Quadruplexes / Q000187:drug effects*; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008958:Models, Molecular; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016615:Telomere
chemical_list: D047028:Macrocyclic Compounds; D010080:Oxazoles; D004247:DNA