Ab initio determination of the flexibility of 2′‐aminoribonucleosides and 2′‐aminoarabinonucleosides inserted in duplexes

The sugar puckering of adenosine and uridine nucleosides with an amino group at 2′ in the ribo or arabino orientations are determined using high‐level quantum mechanical calculations Only the conformations that have dihedrals compatible with their insertion into a duplex are retained. The amino group has always been found to be pyramidal and its orientation governs the conformation of the sugar. The energetically most favorable conformation of the 2′‐aminoribonucleosides has the south puckering but must be discarded. For another orientation of the 2′‐amino group, the conformation is energetically less favorable but has the north puckering. Calculations performed in the presence of a water molecule give similar results but with a smaller energy gap. The model then explains why the insertion of a 2′‐aminoribonucleotide destabilizes double‐stranded RNAs and also double‐stranded DNAs. In the arabino orientation, an NH2 substituent at 2′ favors north puckering. In contrast to 2′‐aminoribonucleosides, deoxynucleosides inserted into a duplex remain in the most energetically favorable conformation compatible with the canonical values of the torsion angles. The whole relaxed potential map, in the amplitude/pseudorotation space, shows that for natural deoxyadenosine there is only one valley in the east running from south to north puckering. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008