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Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B 2 to Duplex DNA
Author(s) -
Zou Tingting,
Kizaki Seiichiro,
Pandian Ganesh N.,
Sugiyama Hiroshi
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201600950
Subject(s) - nucleosome , linker dna , chemistry , dna , histone , linker , duplex (building) , alkylation , microbiology and biotechnology , biophysics , stereochemistry , combinatorial chemistry , biochemistry , biology , computer science , catalysis , operating system
To evaluate the reactivity of antitumor agents in a nucleosome architecture, we conducted in vitro studies to assess the alkylation level of duocarmycin B 2 on nucleosomes with core and linker DNA using sequencing gel electrophoresis. Our results suggested that the alkylating efficiencies of duocarmycin B 2 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 B 2 to duplex DNA could advance its design as an antitumor agent.