| In the first part of this work, we report a simple rule based method for predicting the conformations of oligo- and polysaccharides. The method is based on an exhaustive analysis of the entries in the Cambridge Structural Database (CSD) of crystal structures. We analyzed the values of the critical interglycosidic dihedral angles, O5′-C1′ -OX-CX (phi) and C1′-OX-CX-CX+1 (psi) from all of the entries which ranged from di-, tri-, tetra- and hexa- to octasaccharides. These results were used to construct a second database of dihedral angles. An almost exclusive preference for specific values of phi and psi for a specific type of linkage independent of the context was clearly evident. There was symmetry of placement of the points on the phi-psi plots that was determined by the absolute configuration of the anomeric carbon and the carbon to which the linkage is made. These corresponded to the RR, SS, SR, and RS configurations. Three simple and accurate rules are proposed to help predict the conformations of oligo- and polysaccharides. The results support, expand and generalize earlier reports from other groups.; One of the important methods for determining the three-dimensional structures of carbohydrates is using the proton-carbon hetero-nuclear coupling constant to calculate the critical glycosidic dihedral angle values. In this work we report the synthesis of seven compounds that have rigid glycosidic linkages. These compounds are important to parameterize a new Karplus-type equation. We used these seven compounds and three commercially available molecules to parameterize new Karplus-Type equations relating the vicinal proton-carbon coupling constants, 3JHC, to the glycosidic dihedral angles &phis; (H1′-C1′-OX-CX) and ψ (HX-CX-OX-C1′). The three dimensional structures of the synthetic model compounds 1–7 and the commercially available compounds 8–10 have been refined by Molecular Mechanics and AM1 and PM3 Semi-empirical calculations. The vicinal proton-carbon coupling constants, 3JHC, have been measured in solution by two-dimensional excitation-sculptured indirect-detection experiment (EXSIDE) NMR spectroscopy. From the least squares fitting of the measured coupling constants and the glycosidic dihedral angles of the rigid molecules, new Karplus-type equations of the form: 3JHC (&thetas;) = a Cos 2 (&thetas;) + b Cos (&thetas;) + c, were obtained where &thetas; stands for the dihedral angles defined by the four atoms H-C-O-C (&phis; and ψ for carbohydrates).; Finally, we applied the methods developed in this work in combination with existing methods using multi-nuclear, multidimensional NMR spectroscopy, molecular mechanics calculations and molecular dynamics simulations to study the solution conformations and dynamics of the disaccharide maltose and the tetrasaccharide reduced-maltotetraose, and the pseudo-tetrasaccharide acarbose, which is a potent glycohydrolase inhibitor. |
