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 be obtained by the classical phosphoramidite chemisty starting from protected cyclohexenyl nucleoside building blocks. Incorporation of cylcohexenyl nucleosides in a DNA chain increases the stability of a DNA/RNA hybrid. The complex formed between cyclohexenyl oligoadenylate and its DNA or RNA complement is of similar stability. Circular dichroism (CD) and NMR studies indicate easy conformational adaptation of a cyclohexenyl nucleoside when incorporated in a natural nucleic acid structure. CeNA is stable against degradation in serum and a CeNA/RNA hybrid is able to activate E. Coli RNase H, resulting in cleavage of the RNA strand.