Conformations of cyclic 2',3'-nucleotides and 2',3'-cyclic-5'-diphosphates. Interrelation between the phase angle of pseudorotation of the sugar and the torsions about the glycosyl C(1')-N and the backbone C(4') - C(5') bonds

Abstract

Semiempirical potential energy calculations have been carried out for cyclic 2',3'-nucleotides and their 5'-phosphorylated derivatives, which are the intermediates in the hydrolysis of RNA. Calculations have been performed for both purine and pyrimidine bases for the observed O(1')-endo, O(1')-exo and the unpuckered planar sugar ring conformations. It is found that the mode of sugar pucker largely determines the preferred conformations of these molecules. For cyclic 2',3'-nucleotides themselves, the O(1')-endo sugars show a preference for the syn glycosyl conformation while the O(1')-exo sugars exclusively favor the anti conformation regardless of whether the base is a purine or pyrimidine. For the unpuckered planar sugar, the syn conformation is favored for purines and anti for pyrimidines. Both the gauche (+) (60°) and trans (180°) conformations about the C(4') - C(5') bond are favored for O(1')-endo sugars, while the gauche (-) (300°) and trans (180°) are favored for O(1')-exo sugars. On the contrary, the 5'-phosphorylated cyclic 2',3'-nucleotides of both purines and pyrimidines show a preference for the anti-gauche (+) conformational combination about the glycosyl and C(4') - C(5') bonds for the O(1')-endo sugars and the anti-trans combination for the O(1')-exo sugars. The correlation between the phase angle of the sugar ring and the favored torsions about the glycosyl and the backbone C(4') - C(5') bonds as one traverses along the pseudorotational pathway of the sugar ring is examined.