NMR AND MOLECULAR-MODELING STUDIES OF THE SOLUTION CONFORMATION OF HEPARIN

The solution conformations of heparin and de-N-sulphated, re-N-acetyla ted heparin have been determined by a combination of n.m.r. spectrosco pic and molecular-modelling techniques. The H-1- and C-13-n.m.r. spect ra of these polysaccharides have been assigned. Observed H-1-H-1 nucle ar Overhauser enhancements (n.O.e.s) have been simulated using the pro gram NOEMOL [Forster, Jones and Mulloy (1989) J. Mol. Graph. 7, 196-20 1] for molecular models derived from conformational-energy calculation s; correlation times for the simulations were chosen to fit experiment ally determined C-13 spin-lattice relaxation times. In order to achiev e good agreement between calculated and observed H-1-H-1 n.O.e-s it wa s necessary to assume that the reorientational motion of the polysacch aride molecules was not isotropic, but was that of a symmetric top. Th e resulting model of heparin in solution is similar to that determined in the fibrous state by X-ray-diffraction techniques [Nieduszynski, G ardner and Atkins (1977) Am. Chem. Soc. Symp. Ser. 48, 73 80].