Conformational isomerizations of poly(dA-dT) are dramatically influenced by a substitution of a minor amount of adenine by purine or amino2purine.

We have synthesized poly(dA,dPu-dT) and poly(dA,n2dPu-dT) containing, respectively, 5.7% of purine and 7.4% of amino2purine in place of adenine to demonstrate that these apparently negligible perturbations of the primary structure have dramatic consequences for the polynucleotide conformational isomerizations. The replacement of adenine by amino2purine, preserving the number of hydrogen bonds between the complementary bases, has a stronger effect on the polynucleotide conformational isomerizations than the replacement with purine that is bound only by a single hydrogen bond to thymine. Nevertheless, poly(dA,dPu-dT) forms a more thermostable duplex than poly(dA,n2dPu-dT). Furthermore the few amino2purines in poly(dA,n2dPu-dT) inhibit its isomerization into X-DNA, stabilize but modify A-DNA and stabilize Z-DNA. Kinetics of the B-Z transition of poly(dA,n2dPu-dT) is fast to indicate that the amino groups in the double helix minor groove substantially decrease the kinetic barrier between B- and Z-DNA. On the other hand, the replacement of adenine by purine destabilizes both Z-DNA and A-DNA, and the destabilization of X-DNA is weaker than with amino2purine. A-form and B-form perhaps coexist in poly(dA,dPu-dT) at high concentrations of ethanol.