Single C8-Arylguanine Modifications Render Oligonucleotides in the Z-DNA Conformation under Physiological Conditions

Z-DNA is the only DNA conformation that has a left-handed helical twist. Although Z-DNA has been implicated in both carcinogenesis and mutagenesis, its specific biological role remains uncertain. We have demonstrated that the formation of C8-arylguanine DNA adducts, derived from arylhydrazines, shifts the B/Z-DNA equilibrium toward the Z-DNA conformation in d(CG)5 sequences. However, our previous work examined the effect of two adducts in the duplex, and it was unclear whether the two base modifications were working together to cause the equilibrium shift toward the Z-DNA conformation. Here we report the synthesis and characterization of a hairpin oligonucleotide sequence (d(CG)5T4(CG)5) containing only one C8-arylguanine modified base. The unmodified hairpin and the previously studied unmodified double-stranded oligonucleotide were conformationally similar, and each required ∼3 M NaCl to yield a B-/Z-DNA ratio of 1:1. The introduction of a single C8-arylguanine modification significantly reduced the NaCl...