Cyclohexene nucleic acids (CeNA): Serum stable oligonucleotides that activate RNase H and increase duplex stability with complementary RNA

The replacement of the furanose moiety of DNA by a cyclohexene ring gives a new nucleic acid structure: cyclohexene nucleic acids or CeNA. CeNAs can b e obtained by the classical phosphoramidite chemisty starting from protecte d cyclohexenyl nucleoside building blocks. Incorporation of cylcohexenyl nu cleosides in a DNA chain increases the stability of a DNA/RNA hybrid. The c omplex formed between cyclohexenyl oligoadenylate and its DNA or RNA comple ment is of similar stability. Circular dichroism (CD) and NMR studies indic ate easy conformational adaptation of a cyclohexenyl nucleoside when incorp orated in a natural nucleic acid structure. CeNA is stable against degradat ion in serum and a CeNA/RNA hybrid is able to activate E. Coli RNase H, res ulting in cleavage of the RNA strand.