Adam W, Arnold M A, Grimm G N, Saha-Möller C R, Dall'Acqua F, Miolo G, Vedaldi D
Institute of Organic Chemistry, University of Würzburg, Germany.
Photochem Photobiol. 1998 Oct;68(4):511-8.
We describe the synthesis of a novel psoralen peroxide 1 that generates on irradiation (350 nm) alkoxyl radicals, namely tert-butoxyl radicals, as confirmed by electron spin resonance studies with the spin trap 5,5-dimethyl-pyrroline-N-oxide. The radical source intercalates into the DNA, which has been demonstrated by linear-flow-dichroism measurements. Thus, the alkoxyl radicals are formed advantageously directly in the DNA matrix. In supercoiled pBR322 DNA, the generation of strand breaks by the photochemically or metal-catalyzed generated alkoxyl radicals is demonstrated. Photosensitization by the psoralen chromophore was excluded because similar substances that do not release radicals caused no DNA damage, nor were the photoproducts of the peroxide 1 active. With calf thymus DNA, 8-oxoGua and small amounts of guanidine-releasing products, e.g. oxazolone, were observed. However, in these reactions the photoproduct also displayed some DNA-oxidizing capacity.
我们描述了一种新型补骨脂素过氧化物1的合成，经电子自旋共振研究（使用自旋捕获剂5,5 - 二甲基 - 吡咯啉 - N - 氧化物）证实，该化合物在光照（350 nm）下会产生烷氧基自由基，即叔丁氧基自由基。自由基源可插入DNA中，这已通过线性流动二色性测量得到证实。因此，烷氧基自由基可直接在DNA基质中有利地形成。在超螺旋pBR322 DNA中，证明了光化学或金属催化产生的烷氧基自由基会导致链断裂。由于不释放自由基的类似物质不会造成DNA损伤，且过氧化物1的光产物也无活性，因此排除了补骨脂素发色团的光敏化作用。在用小牛胸腺DNA进行的实验中，观察到了8 - 氧代鸟嘌呤和少量释放胍的产物，如恶唑酮。然而，在这些反应中，光产物也表现出一定的DNA氧化能力。
