A NEW PROGRAM FOR THE CONFORMATIONAL-ANALYSIS BY NMR OF THE SUGAR RING OF NUCLEOSIDES AND NUCLEOTIDES IN SOLUTION - HETROT - APPLICATION TOTHE 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 c oupling constants in natural abundance are discussed, together with th e implementation of a computational algorithm (HETROT) that calculates the range of values of the five parameters describing the conformatio n of the furanose ring (P-N, tau(mN), P-S, tau(mS) and x(N)) that repr oduces all the measured couplings within their estimated errors. HETRO T was applied to the conformational analysis of the sugar ring of 3'-a zido-3'-deoxythymidine (AZT) in DMSO and D2O. In both solvents the sug ar ring exists in fast equilibrium between roughly equally populated N - and S- type conformers. The degree of definition of the precise geom etry of such conformers, and their relative population, that can be ob tained from the experimental data is analysed and graphically presente d.