Structure and Function of Antitumor Ligand-Protein Complex Natural Products

从链霉菌的培养滤液中分离出了一些极有效的烯二炔类抗肿瘤抗生素。虽然这些抗生素被认为是通过环芳构化产生对苯型双自由基，但没有对烯二炔类抗生素产生的碳自由基进行直接EPR测量的报道。C-1027是一种由载脂蛋白和DNA切割烯二炔发色团组成的1:1复合物的粉末，在室温下具有稳定的EPR谱。利用EPR光谱对C1027抗生素中存在的3个顺磁性物质进行了表征。这些自由基由载脂蛋白的对苯型双自由基通过吸氢的动态过程不断提供。本研究结果提供了强有力的证据，证明了烯二炔和对苯形式之间的平衡，以及导致C-1027抗生素自我失活的变质化学机制。

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.