Rademacher Michelle P, Rohn Tim, Haselbach Wiebke, Ott A Theresa, Bringmann Peter W, Gilch Peter
Institut für Physikalische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany.
Cerus Corporation, 1220 Concord Avenue, Concord, CA, 94520, USA.
Photochem Photobiol Sci. 2024 Apr;23(4):693-709. doi: 10.1007/s43630-024-00545-2. Epub 2024 Mar 8.
Psoralens are eponymous for PUVA (psoralen plus UV-A radiation) therapy, which inter alia can be used to treat various skin diseases. Based on the same underlying mechanism of action, the synthetic psoralen amotosalen (AMO) is utilized in the pathogen reduction technology of the INTERCEPT Blood System to inactivate pathogens in plasma and platelet components. The photophysical behavior of AMO in the absence of DNA is remarkably similar to that of the recently studied psoralen 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT). By means of steady-state and time-resolved spectroscopy, intercalation and photochemistry of AMO and synthetic DNA were studied. AMO intercalates with a higher affinity into A,T-only DNA (K = 8.9 × 10 M) than into G,C-only DNA (K = 6.9 × 10 M). AMO covalently photobinds to A,T-only DNA with a reaction quantum yield of Φ = 0.11. Like AMT, it does not photoreact following intercalation into G,C-only DNA. Femto- and nanosecond transient absorption spectroscopy reveals the characteristic pattern of photobinding to A,T-only DNA. For AMO and G,C-only DNA, signatures of a photoinduced electron transfer are recorded.
补骨脂素因光化学疗法（补骨脂素加紫外线A辐射，即PUVA）而得名，该疗法尤其可用于治疗各种皮肤病。基于相同的作用机制，合成补骨脂素氨甲蝶呤（AMO）被用于INTERCEPT血液系统的病原体灭活技术，以灭活血浆和血小板成分中的病原体。在不存在DNA的情况下，AMO的光物理行为与最近研究的补骨脂素4'-氨甲基-4,5',8-三甲基补骨脂素（AMT）非常相似。通过稳态和时间分辨光谱法，研究了AMO与合成DNA的嵌入和光化学性质。AMO嵌入仅含A、T的DNA（K = 8.9×10 M）的亲和力高于仅含G、C的DNA（K = 6.9×10 M）。AMO与仅含A、T的DNA发生共价光结合，反应量子产率为Φ = 0.11。与AMT一样，它嵌入仅含G、C的DNA后不发生光反应。飞秒和纳秒瞬态吸收光谱揭示了与仅含A、T的DNA光结合的特征模式。对于AMO和仅含G、C的DNA，记录到了光诱导电子转移的特征。
