Structure and conformation of the hypermodified purine nucleoside wyosine and its isomers: A comparison of coupling constants and distance geometry solutions

Abstract

AbstractThe structural determination of modified mononucleosides is important for understanding the chemistry, structure and functional changes that they impart to the nucleic acids in which they occur. Empirical analyses of J(HH) couplings have been used to describe nucleoside conformational equilibria for the glycosidic angle (syn‐anti), the C‐4′C‐5′ exocyclic rotamers (gauche+, gauche− and trans) and the sugar pucker (N–S). Distance geometry calculations with distance constraints determined from nuclear Overhauser effects (NOE) should provide equally satisfactory structural information. Proton and carbon chemical shifts and coupling constants were used to describe structural parameters for the tricyclic nucleosides wyosine, 4,9‐dihydro‐4,6‐dimethyl‐9‐oxo‐3‐(β‐D‐ribofuranosyl)imidazo(1,2‐a)purine, and three of its isomers. Using distance geometry calculations with the 14‐19 observed NOEs per nucleoside as distance constraints, multiple structures could be produced with less than 1 Å relative mean standard deviation for the positioning of all atoms. The two methods of structural determination were consistent in their qualitative determination of syn‐anti conformation and sugar pucker.