Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B sub(2) to Duplex DNA

• Published in: Chemistry : a European journal Vol. 22; no. 26; pp. 8756 - 8758
• Main Authors: Zou, Tingting, Kizaki, Seiichiro, Pandian, Ganesh N, Sugiyama, Hiroshi
• Format: Journal Article
• Language: English
• Published: 01.06.2016
• Subjects: Accessibility; Alkylation; Anticancer properties; Assembly; Deoxyribonucleic acid; Electrophoresis; Gene sequencing; In vitro testing
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201600950

To evaluate the reactivity of antitumor agents in a nucleosome architecture, we conducted in vitro studies to assess the alkylation level of duocarmycin B sub(2) on nucleosomes with core and linker DNA using sequencing gel electrophoresis. Our results suggested that the alkylating efficiencies of duocarmycin B sub(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 sub(2) 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 B sub(2) 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 B sub(2) were significantly decreased in core DNA and increased at the histone-free linker DNA sites compared with naked DNA conditions.