Guillo L A, Blais J, Vigny P, Spassky A
Laboratoire de Physique et Chimie Biomoléculaires, Institut Curie, Paris, France.
Photochem Photobiol. 1995 Apr;61(4):331-5. doi: 10.1111/j.1751-1097.1995.tb08617.x.
It has been recently shown that UVA (320-400 nm) irradiation of DNA in the presence of pyridopsoralens induces the formation of thymine cyclobutane dimers in addition to monoadducts. In this work, we measured the potency of a saturated pyridopsoralen to photosensitize DNA, despite its inability to covalently attach to DNA. First, from spectroscopic fluorescence measurements, we have shown that both analogs, saturated and unsaturated pyridopsoralens, namely 4',5'-dihydro-7-methyl-pyrido[3,4-c]psoralen (DH-MePyPs) and 7-methylpyrido[3,4-c]psoralen, exhibit a similar global affinity for DNA. Secondly, we demonstrated, by footprinting experiments, that exposure of a DNA sequence to 365 nm UV radiation in the presence of DH-MePyPs results in selective cyclobutane thymine dimerization. Thymines located in the immediate proximity of the 5'-TA-3' step are exclusively affected and the frequency of this photoprocess depends on flanking sequences. We thus probe a selective thymine dimer photosensitizer. Results are discussed in terms of drug affinity and physical properties of the helix at the binding site.
最近研究表明，在吡啶补骨脂素存在的情况下，DNA受到UVA（320 - 400纳米）照射时，除了形成单加合物外，还会诱导胸腺嘧啶环丁烷二聚体的形成。在这项工作中，我们测量了一种饱和吡啶补骨脂素对DNA的光敏化能力，尽管它无法与DNA共价结合。首先，通过光谱荧光测量，我们表明饱和和不饱和吡啶补骨脂素这两种类似物，即4',5'-二氢-7-甲基-吡啶并[3,4-c]补骨脂素（DH-MePyPs）和7-甲基吡啶并[3,4-c]补骨脂素，对DNA表现出相似的整体亲和力。其次，我们通过足迹实验证明，在DH-MePyPs存在的情况下，DNA序列暴露于365纳米紫外线辐射会导致选择性的环丁烷胸腺嘧啶二聚化。紧邻5'-TA-3'步的胸腺嘧啶受到专门影响，并且这种光过程的频率取决于侧翼序列。因此，我们探究了一种选择性胸腺嘧啶二聚体光敏剂。根据药物亲和力和结合位点处螺旋的物理性质对结果进行了讨论。
