Guanosine analog with respect to Z-DNA stabilization: Nucleotide with combined C8-bromo and C2'-ethynyl modifications

The stabilization of left-handed Z-DNA double strands by chemical modifications is especially of interest regarding investigations of its biological role. Incorporation of modified nucleotide building blocks in DNA allows recognition studies under physiological conditions without the need for a Z-DNA inducing environment. Approaches to enforce the Z-DNA double helix using guanosine derivatives are the introduction of sterically demanding groups at guanine C8 or of 2'-ribosyl substitutions determining the ribosyl conformation. 8-Bromo-2'-ethynyl-arabino-deoxyguanosine was synthesized as phosphoramidite building block. Incorporated in suitable oligonucleotides the potential to induce the Z-form DNA was investigated by CD spectroscopy. With a nucleotide containing the 8-bromo and the 2'-ethynyl group a synergistic effect of the two modifications was expected to provide stronger stabilization of Z-DNA.