2'5'-linked polynucleotides do form a double-stranded helical structure: a result from the energy minimization study of A2'p5'A.

Abstract

AbstractExperimental results on 2′5′‐linked subunit systems of nucleic acids are interpreted to substantiate the view that the 2′5′‐linked polynucleotides cannot form double‐stranded helical structures. In order to look into this aspect of the 2′5′‐linked units, as well as to make a detailed comparison between the conformational characteristics of 3′5′‐ and 2′5′‐linked systems, we carried out an exhaustive theoretical study on A2′p5′A. The method was to compute the various terms of energy contributions to a conformational state and then to minimize the total energy, permitting all the relevant dihedral angles to adjust themselves. Four hundred thirty two probable starting conformations were considered for this treatment, but we found only 10 of them to come under low‐energy states, i.e., within 5 kcal/mol energy difference with reference to the global minimum energy state. The characteristic properties of these 10 conformations were compared in detail with those previously obtained on the corresponding 3′5′‐linked subunit, as well as such units with other base sequences. As a further step, a model‐building study was undertaken. Using the backbone‐course, base‐stacking, and hydrogen‐bonding possibilities of the 10 low‐energy conformations of the dimer A2′p5′A, double‐stranded helical structures were scrutinized for the 2′5′‐linked polynucleotide. Of a few reasonable forms, a right‐handed duplex structure satisfied our requirements. We describe this new duplex, making comparisons with the standard A‐ and B‐form states of DNA. The available experimental and theoretical results on 2′5′‐linked systems are also analyzed.