DNA interstrand crosslink in mammalian cell involves several targets, for instance as anticancer agents, many of anticancer agents such as mitomycin C, nitrogen mustard, and chlorambucil, can kill cancer cells by alkylating DNA opposing strands. We have introduced coumarin triazol groups into thymidine, cytidine and adenine starting from the azide-modified derivatives by using click chemistry which forms copper-(I)-catalyzed 1,2,3-triazol from azides and terminal alkyne resulted in compounds 1a -c.  Click reactions, preceded smoothly with the alkyne modified coumarin leading to 1a-c  in excellent yields.The corresponding phosphoamidites 2a-c  have been synthesized and incorporated into oligonucleotides. The effect of 1a -c on duplex stability has been investigated and their cross-linking ability has been determined. Finally, photoswitchable DNA interstrand cross-link has been developed. This crosslinking reaction is induced by coumarin modified nucleoside (1) with the corresponding non�modified nucleoside in the complementary strand by [2+2] photo-cycloadditiion. The modification of pyrimidines by �click� reaction expanded the opportunities for developing new approach toward the synthesis of modified DNA via solid-phase oligonucleotide synthesis. Coumarin-labeled ssDNA could be used as a primer to produce DNA sequencing products and laser-induced fluorescence detection. Photoswitchable crosslinking formation by Coumarin which was never been exploited for coumarin in the DNA sequences.

Photoswitchable coumarin induced DNA interstrand cross-link construction by click modified nucleotide

247th National Meeting (2014)

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