title: Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B2 to Duplex DNA.
abstract: To evaluate the reactivity of antitumor agents in a nucleosome architecture, we conducted in vitro studies to assess the alkylation level of duocarmycin B2 on nucleosomes with core and linker DNA using sequencing gel electrophoresis. Our results suggested that the alkylating efficiencies of duocarmycin B2 were significantly decreased in core DNA and increased at the histone-free linker DNA sites when compared with naked DNA conditions. Our finding that nucleosome assembly alters the accessibility of duocarmycin B2 to duplex DNA could advance its design as an antitumor agent.
authors.affiliation: Department of Science, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8501, Japan.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zou
authors.affiliation: Department of Science, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8501, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kizaki
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo, Kyoto, 606-8502, Japan.
authors.forename: Ganesh N
authors.initials: GN
authors.lastname: Pandian
authors.affiliation: Department of Science, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8501, Japan. hs@kuchem.kyoto-u.ac.jp.|Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo, Kyoto, 606-8502, Japan. hs@kuchem.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000478:Alkylation; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D000080890:Duocarmycins; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011760:Pyrrolidinones / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000080890:Duocarmycins; D007211:Indoles; D009707:Nucleosomes; D011760:Pyrrolidinones; C060649:duocarmycin B2; D004247:DNA
keywords: accessibility; alkylation; antitumor agents; duocarmycin B2; nucleosome