Structure and Function of Antitumor Ligand-Protein Complex Natural Products

从链霉菌属的培养物中分离出了许多非常有效的烯二炔类抗肿瘤抗生素。虽然这些抗生素被认为通过环芳构化产生对苯炔型双自由基，但还没有报道烯二炔抗生素产生的碳自由基物质的直接EPR测量。色蛋白抗生素C-1027是由载体脱辅基蛋白和切割DNA的烯二炔发色团组成的1：1复合物的粉末，在室温下显示稳定的EPR谱。我们用EPR谱表征了C1027抗生素中存在的三种顺磁性物种。这些自由基种类通过对苯炔型双自由基从脱辅基蛋白中夺氢的动态过程不断提供。目前的结果提供了强有力的证据之间的平衡，烯二炔和对苯炔形式，以及化学机制的恶化，导致自失活的C-1027抗生素。

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.