Efficient Incorporation of a Copper Hydroxypyridone Base Pair in DNA

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Abstract
Recently, we reported the first artificial nucleoside for alternative DNA base pairing through metal complexation (J. Org. Chem.1999, 64, 5002−5003). In this regard, we report here the synthesis of a hydroxypyridone-bearing nucleoside and the incorporation of a neutral Cu2+-mediated base pair of hydroxypyridone nucleobases (H−Cu−H) in a DNA duplex. When the hydroxypyridone bases are incorporated into the middle of a 15 nucleotide duplex, the duplex displays high thermal stabilization in the presence of equimolar Cu2+ ions in comparison with a duplex containing an A−T pair in place of the H−H pair. Monitoring temperature dependence of UV-absorption changes verified that a Cu2+-mediated base pair is stoichiometrically formed inside the duplex and dissociates upon thermal denaturation at elevated temperature. In addition, EPR and CD studies suggested that the radical site of a Cu2+ center is formed within the right-handed double-strand structure of the oligonucleotide. The present strategy could be developed for controlled and periodic spacing of neutral metallobase pairs along the helix axis of DNA.