A new program for the conformational analysis by NMR of the sugar ring of nucleosides and nucleotides in solution: HETROT. Application to the sugar ring of AZT in solution

A new program for the conformational analysis by NMR of the sugar ring of nucleosides and nucleotides in solution, based on both 1H- 1H and long range 1H- 13C coupling constants is presented. The experimental conditions for the accurate measurement of long range heteronuclear coupling constants in natural abundance are discussed, together with the implementation of a computational algorithm (HETROT) that calculates the range of values of the five parameters describing the conformation of the furanose ring (pn, τmN, PS, τmS, τmS and xN) that reproduces all the measured couplings within their estimated errors. HETROT was applied to the conformational analysis of the sugar ring of 3′-azido-3′-deoxylhymidine (AZT) in DMSO and D2O. In both solvents the sugar ring exists in fast equilibrium between roughly equally populated N- and S- type conformers. The degree of definition of the precise geometry of such conformers. and their relative population, that can be obtained from the experimental data is analysed and graphically presented.