title: Synthesis and biological properties of pyrrole-imidazole polyamide conjugates.
abstract: We have developed a series of conjugates between pyrrole (Py)-imidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H benz[e]indole (seco-CBI) with an indole linker. High resolution polyacrylamide gel electrophoresis revealed that these conjugates alkylated DNA at predetermined sequences. Then, we demonstrated that conjugates 1 and 2 have DNA alkylation activities at double stranded human telomere sequence and potent cytotoxicities in cancer cell lines. In addition, we showed that conjugate 3 alkylates DNA with ten-base-pair recognition sequence in the presence of partner polyamide 4, which suggested alkylation through 3-4 heterodimer formation.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo, Kyoto 606-8502, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Minoshima
authors.forename: Shunta
authors.initials: S
authors.lastname: Sasaki
authors.forename: Jun
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000478:Alkylation; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles