QUANTUM MOLECULAR MODELING OF HYALURONAN

Molecular modeling of the secondary structure of hyaluronan is present ed on the basis of the following molecular models: GlcA, GlcNAc, GlcA 1 --> 3 GlcNAc, GlcNAc 1 --> 4 GlcA, GlcNAc 1 --> 4 GlcA 1 --> 3 GlcNA c and GlcA 1 --> 3 GlcNAc 1 4 GlcA, The optimized geometries of the mo nosaccharides obtained using AM1 and ab initio STO-3G methods are in g ood agreement with the crystallographic data. The flexibility of the b eta 1 --> 3 and beta 1 --> 4 linkages was studied using AM1 and ab ini tio HF/3-21G methods. Our study shows that in all cases the beta 1 --> 3 linkage is more flexible than the beta 1 --> 4 linkage, The minimal energy conformations of the di- and trisaccharides studied correspond to a compact conformation for the beta 1 --> 3 linkage and to standar d conformations in agreement with the left-handed helices of sodium hy aluronate or calcium hyaluronate, The electrostatic properties and the frontier orbital characteristics obtained at the HF/3-21G level are d iscussed. (C) 1997 Elsevier Science B.V.