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 H-1-H-1 and long range H-1-C-13 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 (P-N, tau(mN), P-S, tau(mS) and x(N)) 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'-deoxythymidine (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.