120(P64) 抗腫瘍性抗生物質レイナマイシンによるDNAアルキル化反応(ポスター発表の部)

概要

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The mode of action of a new class of sulfur-containing antitumor antibiotic leinamycin (1) is presented. Our earlier studies have shown that leinamycin causes DNA-cleavage in the presence of thiols. In the course of our efforts to identify the mechanism of DNA-cleavage, we obtained leinamycin-N7 guanine adduct (3) from the DNA treated with thiol-activated leinamycin. Sequencing gel analysis of the DNA showed the guanine specific alkylation by this agent. From the structures of the guanine adduct and other degradation products, we propose that the nucleophilic attack of thiol at the S-2' sulfur atom of the 1,3-dioxo-1,2-dithiolane moiety triggers off the conversion of leinamycin to an electrophilic molecule, presumably episulfonium species (8), which is responsible for DNA-alkylation and subsequent DNA-cleavage by leinamycin.
天然有機化合物討論会の論文
1996-09-02