Stereochemistry of 2′,5′ Nucleic Acids and Their Constituents

Abstract

Shape and dimension of the preferred nucleotide repeats in nucleic acids are found to depend on whether the sugar-phosphate linkage is of 2′,5′ or 3′,5′ type. It is shown that a nucleotide which is “compact” in 3′,5′ nucleic acids is rendered “extended” and vice versa for a given sugar pucker. It is interesting that this feature is accompanied by a switch in the preferred sugar ring conformation in 3′,5′ and 2′,5′ nucleic acids. 3′ ribose and 3′ deoxyribose rings (in 2′,5′ linkages) tend to favour C2′ endo and C3′ endo puckers respectively in contrast to C3′ endo and C2′ endo puckers favored by 2′ ribose and 2′ deoxyribose sugars (in 3′,5′ linkages).The distinguishable features between the nucleotide repeats of 3′,5′ and 2′,5′ nucleic acids need to be recognised while discussing their structural properties, as well as those of a variety of complexes that could be formed involving 2′,5′ and 3′,5′ strands of DNA and RNA. Ability and stability, or lack of them, for formation of a specific combination of these complexes may be directly related to the stereochemical constraints imposed as a consequence of conformationally homogeneous or heterogeneous nature of the repeating nucleotides of the complexing chains. As a first step towards delineating stereochemical features that distinguish 2′,5′ nucleic acids from their naturally occurring isomer A and B type helices have been modelled using the new concept of “compact” and “extended” nucleotide repeat that seemingly unifies helix generation of both types of linkages. Helical models for 2′,5′ RNA with “dinucleotide” repeat based on the crystal structure of 2′,5′ ApU have also been obtained.