Sugiura, Yukio and Shiraki, Takashi and Konishi, Masataka and Oki, Toshikazu (1990) DNA intercalation and cleavage of an antitumor antibiotic dynemicin that contains anthracycline and enediyne cores. Proceedings of the National Academy of Sciences of the United States of America, 87 (10). pp. 3831-3835. ISSN 0027-8424 http://resolver.caltech.edu/CaltechAUTHORS:SUGpnas90
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Dynemicin is a hybrid containing anthraquinone and enediyne cores, which contribute to binding and cleavage of DNA, respectively. DNA strand scission by the antitumor antibiotic is significantly enhanced by the addition of NADPH or thiol compounds. The preferential cutting site of dynemicin is on the 3' side of purine bases (i.e., 5'-GC, -GT, and -AG) and is clearly different from the cutting sites of esperamicin and calicheamicin. The double-stranded and the stem regions of single-stranded DNAs are preferentially cleaved by dynemicin. Therefore, dynemicin may be a useful reagent for probing secondary structures of DNA. Pretreatment of DNA with Adriamycin and actinomycin D alters the cutting mode of dynemicin. Dynemicin-mediated DNA breakage is strongly inhibited by pretreatment of the DNA with distamycin A and anthramycin, suggesting that dynemicin interacts with the minor groove of the DNA helix. Intercalation of the anthraquinone core into the DNA followed by the attack of the phenyl diradical formed from the enediyne core is considered as a possible mechanism of action of dynemicin.
|Additional Information:||Copyright © 1990 by the National Academy of Sciences. Communicated by Samuel J. Danishefsky, February 26, 1990 (received for review October 1, 1989). We are grateful to Drs. T. W. Doyle and D. R. Langley for pertinent discussion of DNA cleaving mechanisms. This study was supported in part by Grant-in-Aid for Scientific Research on Priority Area from the Ministry of Education, Science, and Culture, Japan. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.|
|Subject Keywords:||hybrid antibiotic; nucleotide specificity; minor groove; action mechanism|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||26 Jan 2006|
|Last Modified:||26 Dec 2012 08:44|
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