| Budget Amount *help |
¥38,650,000 (Direct Cost: ¥37,600,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2001: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2000: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1999: ¥28,500,000 (Direct Cost: ¥28,500,000)
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| Research Abstract |
A number of extremely potent enediyne antitumor antibiotics have been isolated from culture filtrates of Streptomyces species. Although these antibiotics are believed to generate p-benzyne-type biradicals through cycloaromatization, no direct EPR measurements of carbon radical species generated from enediyne antibiotics have been reported. A chromoprotein antibiotic, C-1027, which is powder of a 1 : 1 complex composed of a carrier apoprotein and a DNA cleaving enediyne chromophore, shows a steady EPR spectrum at room temperature. We characterized three paramagnetic species existing in C1027 antibiotic by EPR spectroscopy. These radical species are supplied constantly by dynamic processes through hydrogen abstraction by p-benzyne type biradical from the apoprotein. The present results provide strong evidence for equilibration between the enediyne and p-benzyne form, as well as a chemical mechanism of deterioration leading to self-inactivation of the C-1027 antibiotic.
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