Conformational Isomerizations of Poly(dA-dT) Are Dramatically Influenced by a Substitution of a Minor Amount of Adenine by Purine or Amino²purine

Abstract

We have synthesized poly(dA,dPu-dT) and poly(dAn²dPu-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.