NMR Structure of a 2′,5′ RNA Favors A Type Duplex with Compact C2′endo Nucleotide Repeat

Abstract

In order to provide a structural basis for the unusual properties of 2′,5′ nucleic acids, especially their unsuitability as information molecules, we report here a high resolution NMR structure of a 2′,5′ RNA fragment r(GCCGCGGC). It forms an A type duplex with C2′endo compact nucleotide repeat, instead of the familiar C3′endo compact nucleotide (seen in RNA) supporting the deductions made earlier from stereochemical considerations. This data together with the observation that 2′,5′ nucleic acids require mandatory slide and displacement for duplex and triplex structure formation suggest their reluctance to form the biologically relevant B type duplex. It is argued that this lack of flexibility for helical polymorphism and other inadequacies as a consequence of this may be a contributing factor for the rejection of 2′,5′ links by nature. The structure exhibits interesting features such as the syn glycosyl conformation for the terminal guanine and a hydrogen bond between O3′ hydroxyl and anionic oxygen of the phosphate.