Nickel and cobalt reagents promote selective oxidation of Z-DNA

The structural characteristics of Z-DNA were used to challenge the selectivity of guanine oxidation promoted by nickel and cobalt reagents. Base pairing and stacking within all helical structures studied previously had hindered access to guanine and limited its reaction. However, the Z-helix uniquely retains high exposure of guanine N7. This exposure was sufficient to direct oxidation specifically to a plasmid insert -(CG)(13)AATT(CG)(13)- that adopted a Z-conformation under native supercoiling. An alternative insert -(CG)(7)- retained its B-conformation and demonstrated the expected lack of reactivity. For a nickel salen complex made from a particularly bulky ligand, preferential reaction shifted to the junctions within the Z-DNA insert as is common for large reagents. Inactivation of the nickel reagents by high-salt concentrations prevented parallel investigations of Z-DNA, formed by oligonucleotides. However, the activity of Co(2+) was minimally affected by salt and consequently confirmed the high reactivity of 5'-p(CG)(4) in its Z-conformation. These reagents may now be applied to a broad array of targets, since their structural specificity remains predictable for both complex and helical assemblies of nucleic acids.