2-Oxoalkyl caged oligonucleotides: one-electron reductive activation into emergence of ordinary hybridization property by hypoxic X-irradiation.

Ionizing radiation triggers the activation of caged oligodeoxynucleotides (ODNs) with a 2-oxoalkyl leaving group to give the corresponding normal uncaged strands. We designed and synthesized ODNs caged by a 2-oxopropyl group at a given thymine N(3) position (d(oxo)T) to evaluate their one-electron reduction characteristics. Upon hypoxic X-radiolysis in aqueous solution, the caged ODNs released the 2-oxopropyl group to produce the corresponding uncaged ODNs. Digestion by a restriction enzyme Swa I revealed that caged ODN pre-irradiated in hypoxia could form an ordinary duplex with its complementary strand.

Regulation of DNA duplex formation by hypoxic irradiation: one-electron reduction characteristics of oligodeoxynucleotides possessing 2-oxoalkyl functional group.

We synthesized oligodeoxynucleotides (ODN) possessing 2-oxoalkyl group on thymidine (d(oxo)T) to characterize the radiolytic reduction in aqueous solution. Corresponding unmodified ODNs were generated from ODNs containing d(oxo)T upon hypoxic irradiation. Enzymatic digestion of the duplex consisting of the hypoxically irradiated ODN containing d(oxo)T and its complementary strand resulted in an efficient cleavage, but no cleavage was observed when a control duplex was digested without irradiation.

Effects of structural modification on the DNA binding properties and photo-induced cleavage reactivity of propargylic sulfones conjugated with an anthraquinone structure.

Propargylic sulfones are known as pH-dependent DNA cleaving agents. We have designed a novel propargylic sulfone conjugated with an anthraquinone structure and evaluated its DNA binding and cleavage characteristics. The propargylic sulfone 3 showed high intercalating ability attributable to anthraquinone chromophore, leading to the efficient alkylation of DNA. The anthraquinone chromophore in 3 also acted as a photosensitizer, and photoirradiation of 3 with DNA induced one-electron oxidation, resulting in the further DNA cleavage. Evaluation of the effect of 3 against EMT6/KU cells revealed that 3 exhibited potent cytotoxicity, even without photoirradiation.