title: Sequence-specific alkylation by a tandem motif of pyrrole-imidazole CBI conjugate.
abstract: We have developed various types of sequence-specific alkylating agents by conjugation of Py-Im polyamides and alkylating moieties 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) with an indole linker. In order to extend the length of target DNA sequence of the hairpin Py-Im polyamide 1, we designed and synthesized Y-shaped and tandem hairpin Py-Im polyamides 2 and 3. High-resolution denaturing polyacrylamide gel electrophoresis using 5'-Texas Red-labeled 465-bp DNA fragments revealed that conjugates 2 and 3 alkylated the adenine of target DNA sequences at nanomolar concentrations. Furthermore, evaluation in human cancer cell lines revealed that these Py-Im polyamides 2 and 3 have strong cytotoxicities.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Shunta
authors.initials: S
authors.lastname: Sasaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Minoshima
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* / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007211:Indoles; D011758:Pyrroles