Zein N, Sinha A M, McGahren W J, Ellestad G A
Infectious Disease Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.
Science. 1988 May 27;240(4856):1198-201. doi: 10.1126/science.3240341.
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.
加利车霉素γ1I是一种最近发现的含二炔-烯的抗肿瘤抗生素，对鼠类肿瘤有相当强的效力。在体外，这种药物在小沟中与双螺旋DNA相互作用，并导致位点特异性双链切割。有人提出，观察到的切割特异性是药物与DNA独特契合的结果，随后产生一种不可扩散的1,4-脱氢苯双自由基物种，该物种通过从脱氧核糖环上夺取氢引发氧化链断裂。加利车霉素γ1I在极低浓度下引起双链切割的能力可能解释了它强大的抗肿瘤活性。
