Quantum molecular modeling of hyaluronan

Abstract Molecular modeling of the secondary structure of hyaluronan is presented on the basis of the following molecular models: GlcA , GlcNAc , GlcA 1 → 3 GlcNAc , GlcNAc 1 → 4 GlcA , GlcNAc 1 → 4 GlcA 1 → 3 GlcNAc and GlcA 1 → 3 GlcNAc 1 → 4 GlcA . The optimized geometries of the monosaccharides obtained using AM1 and ab initio STO-3G methods are in good agreement with the crystallographic data. The flexibility of the β 1 → 3 and β 1 → 4 linkages was studied using AM1 and ab initio HF/3-21G methods. Our study shows that in all cases the β 1 → 3 linkage is more flexible than the β 1 → 4 linkage. The minimal energy conformations of the di- and trisaccharides studied correspond to a compact conformation for the β 1 → 3 linkage and to standard conformations in agreement with the left-handed helices of sodium hyaluronate or calcium hyaluronate. The electrostatic properties and the frontier orbital characteristics obtained at the HF/3-21G level are discussed.

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