Short oligonucleotide prodrug having 5-fluoro and 5-iodouracil inhibits the proliferation of cancer cells in a photo-responsive manner.
Photo-induced C1' hydrogen abstraction of 5-fluoro-2'-deoxyuridine was adopted as the key reaction for releasing 5-fluorouracil (5-FU) anticancer drug from oligonucleotide strands. After photoirradiation following 5-FU release, anticancer activity was expected. We demonstrated that oligonucleotide tetramer, d(A(F)U(I)UA), can release 5-FU under physiological conditions in a photo-responsive manner thorough photo-induced C1' hydrogen abstraction, and that the 5-FU released from d(A(F)U(I)UA) having a phosphorothioate backbone clearly suppresses the proliferation of HeLa cells in a photo-responsive manner.