X-ray structure of a dinucleoside monophosphate A2'p5'C that contains a 2'-5' link found in (2'-5')oligo(A)s induced by interferons: single-stranded helical conformation of 2'-5'-linked oligonucleotides

Abstract

In order to understand why DNA and RNA have the 3'-5' and not the 2'-5' link and to delineate the stereochemistry of the 2'-5' phosphodiester links, we crystallized and carried out a very accurate x-ray diffraction analysis of A2 p5'C, an analog of A2' p5'A. Contrary to numerous reports in the literature that conclude that the tendency for 2'-5' nucleotides to stack intramolecularly is stronger than for 3'-5' counterparts, we find hardly any intramolecular base stacking for this molecule but find an intramolecular "stacking" of the ribose oxygen-4' of cytidine on top of the adenine ring. Although A2' p5'C shows the standard conformational features usually found for 3'-5' nucleotides, the overall stereochemistry of 2'-5' nucleotides is quite different because the 2' link orients the backbone inwards to the bases unlike the 3' and 5' links that orient it away from the bases. With the conformational features found for A2' p5'C, it is possible to build a very compact right-handed single-stranded helix but not a double helix. Such a preference for single-stranded helices may be the reason for the absence of 2'-5' bonds in DNA and RNA even though the 2'-5' bonds are formed more readily then 3'-5' bonds.