Häcker Sebastian, Schrödter Maren, Kuhlmann Arthur, Wagenknecht Hans-Achim
Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
JACS Au. 2023 May 26;3(7):1843-1850. doi: 10.1021/jacsau.3c00167. eCollection 2023 Jul 24.
The direct and sequence-dependent investigation of photochemical processes in DNA on the way to cyclobutane pyrimidine dimers (CPDs) as DNA damage requires the probing by photochemically different photosensitizers. The C-nucleosides of xanthone, thioxanthone, 3-methoxyxanthone, and triphenylene as photosensitizers were synthesized by Heck couplings and incorporated into ternary photoactive DNA architectures. This structural approach allows the site-selective excitation of the DNA by UV light. Together with a single defined site for T-T dimerization, not only the direct CPD formation but also the distance-dependent CPD formation in DNA as well as the possibility for energy transport processes could be investigated. Direct CPD formation was observed with xanthone, 3-methoxyxanthone, and triphenylene as sensitizers but not with thioxanthone. Only xanthone was able to induce CPDs remotely by a triplet energy transfer over up to six intervening A-T base pairs. Taken together, more precise information on the sequence dependence of the DNA triplet photochemistry was obtained.
在研究DNA光化学过程生成环丁烷嘧啶二聚体（CPD）作为DNA损伤的过程中，对光化学过程进行直接且依赖序列的研究需要使用光化学性质不同的光敏剂进行探测。通过Heck偶联反应合成了呫吨酮、噻吨酮、3-甲氧基呫吨酮和三亚苯的C-核苷作为光敏剂，并将其纳入三元光活性DNA结构中。这种结构方法允许通过紫外光对DNA进行位点选择性激发。结合T-T二聚化的单个定义位点，不仅可以研究DNA中直接CPD的形成，还可以研究距离依赖性CPD的形成以及能量传输过程的可能性。以呫吨酮、3-甲氧基呫吨酮和三亚苯作为敏化剂时观察到了直接CPD的形成，但以噻吨酮作为敏化剂时未观察到。只有呫吨酮能够通过三重态能量转移在多达六个中间A-T碱基对的距离上远程诱导CPD。综上所述，获得了关于DNA三重态光化学序列依赖性的更精确信息。
