Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B2 to Duplex DNA

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. Nucleosome assembly influence: In vitro studies aimed at evaluating the alkylation level of duocarmycin B2 on nucleosomes with core and linker DNA were conducted using sequencing gel electrophoresis. The results suggested that, in the nucleosome structure, the alkylating efficiencies of duocarmycin B2 were significantly decreased in core DNA and increased at the histone‐free linker DNA sites compared with naked DNA conditions.