N-Acetyl Calicheamicin g1

Calicheamicins are a group of enediyne antitumor antibiotics. Calicheamicins target DNA and cause strand scission. Story behind Calicheamicns: In the mid 1980’s a Lederle Lab scientist was on vacation in Texas and took a chalky soil sample from an area near the town of Kerrville that the locals call the “calichi pits”. Back in the lab a strain of the Actinomycete bacteria, Micromonospora echinospora, was isolated from this soil sample and was found to produce a novel antibiotic later named calicheamicin. Calicheamicin is fabulously potent. The good news was that only a couple of calicheamicin molecules could easily kill a cancer cell (almost totally unheard of in efficacy and a thousand times more potent than some of the best clinical antitumor drugs, like adriamycin). The bad news was that only a couple of calicheamicin molecules could also easily kill a normal cell. In fact, calicheamicin kills everything it touches: bacteria, fungi and viruses, eukaryotic cells and eukaryotic organisms like mice and people. Studies on calicheamicin by George Ellestad and Nada Zein, who among other scientists at at Lederle Laboratories*, showed why calicheamicin was so fabulously potent: it had a highly unusual mode of action. Calicheamicin acts as a “chemical nuclease”. Calicheamicin is similar to an enzyme (it’s really a chemical catalyst); it is able to repeatedly bind to DNA and make double strand breaks. Exposure to just a few molecules of calichaemicin can chop an entire genome