Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically.
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.
Zein
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Infectious Disease Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.
Sinha
A M
AM
McGahren
W J
WJ
Ellestad
G A
GA
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic; D001483:Base Sequence; D004247:DNA; D004249:DNA Damage; D004278:DNA, Superhelical; D053281:Enediynes; D008969:Molecular Sequence Data; D010100:Oxygen; D013379:Substrate Specificity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004278:DNA, Superhelical; D053281:Enediynes; C055955:calicheamicin gamma(1)I; D004247:DNA; D010100:Oxygen