Protected 32P-Labels in Deoxyribonucleotides: Investigation of Sequence Selectivity of DNA Photocleavage by Enediyne-, Fulvene-, and Acetylene-Lysine Conjugates

摘要

Since natural and synthetic photosensitizers can generate reactive intermediates on demand with a high degree of temporal and spatial control, they attract considerable interest as molecular tools for the modification of DNA.[1] Bis-tetrafluoropyridinyl (bis-TFP) enediynes are attractive organic DNA photocleavers because they do not require metals or reducing agents and because they are thermally and photochemically stable unless excited in the vicinity of a suitable electron donor such as DNA. Thus, not only light but also binding to DNA are necessary for the activation. Photoinduced electron transfer (PET) triggers transformation of these molecules into indenes (the C1-C5 cyclization, Scheme 1) with four concomitant formal H-atom abstractions.[2] In addition, bis-TFP enediynes can be excited with low-energy visible light under two-photon conditions,[3] the cyclization can be effectively controlled by substituents,[4] and, unlike the Bergman cyclization,[5], [6] individual steps in the C1-C5 cascade can lead to DNA photocleavage through either oxidative or hydrogen-abstraction mechanisms. Intriguingly, the nature of the reaction products suggests that reactivation of fulvene intermediates can lead to further DNA damage that develops after the cyclization step.