Thymine methyl groups stabilize the putative A-form of the synthetic DNA poly(amino2dA-dT)

Poly(amino2dA-dT) easily isomerizes into a non-B conformer which most authors think is an A-form. We synthesized new DNA analogs poly(amino2dA-ethyl5dU) and poly(amino2dA-dU) to show that they do not prefer this conformer. Hence the putative A-form is, like Z-DNA of poly(dG-dC) but unlike A-DNA, strongly stabilized by the methyl group in position 5 of the pyrimidine base. In addition, the putative A-form is induced by divalent cations while it does not need any alcohol to be stable, both properties being typical for Z-DNA again but quite unusual with A-DNA. Despite these similarities, the putative A-form is also distinct from Z-DNA, as poly(amino2dA-dT) is shown to isomerize into a Z-form in the NaCl + NiCl2 solvent system like poly(dA-dT). The present data indicate that the putative A-form of poly(amino2dA-dT) differs in a significant way from all canonical conformers of DNA. Furthermore, the studies of the poly(amino2dA-dT) family of polydeoxynucleotides reveal a novel type of conformational switch in DNA. We also report the B-Z transitions of poly(amino2dA-ethyl5dU) and poly(amino2dA-dU) and their transitions into the putative A-form in aqueous alcohol solutions.