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Science 27 May 1988:
Vol. 240. no. 4856, pp. 1198 - 1201
DOI: 10.1126/science.3240341
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Articles

Science, Vol 240, Issue 4856, 1198-1201
Copyright © 1988 by American Association for the Advancement of Science

articles

Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically

N Zein, AM Sinha, WJ McGahren, and GA Ellestad

Infectious Disease Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.

Calicheamicin gamma 1I is a recently discovered diyne-ene--containing antitumor antibiotic with considerable potency against murine tumors. In vitro, this drug interacts with double-helical DNA in the minor groove and causes site-specific double-stranded cleavage. It is proposed that the observed cleavage specificity is a result of a unique fit of the drug and DNA followed by the generation of a nondiffusible 1,4-dehydrobenzene--diradical species that initiates oxidative strand scission by hydrogen abstraction on the deoxyribose ring. The ability of calicheamicin gamma 1I to cause double-strand cuts at very low concentrations may account for its potent antitumor activity.


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