Examination of the effect of structural variation on the N-glycosidic torsion (PhiN) among N-(beta-D-glycopyranosyl)acetamido and propionamido derivatives of monosaccharides based on crystallography and quantum chemical calculations.

GlcNAcbetaAsn linkage is conserved in the N-glycoproteins of all eukaryotes. l-Glutamine (Gln), which is a one carbon higher homolog of Asn, is never glycosylated. X-ray crystallographic study of several beta-1-N-acetamido- and propionamido derivatives of monosaccharides has earlier shown that the N-glycosidic torsion, Phi(N), is influenced to a larger extent by the structural variation of the sugar part than that of the aglycon moiety. In order to examine the influence of the carbohydrate pendent groups on the conformational preference of the N-glycosidic linkage with respect to Phi(N,) several models and analogs with gluco and manno configuration have been studied in the present work by computational chemistry. The crystal structure of XylbetaNHPr is reported here and its molecular packing compared with related analogs. The conjunction of combining Crystallographic and computational studies allows to demonstrate the strong influence that the group at C2, and environmental factors particularly inter- and intramolecular interactions involving regular hydrogen bonds and the weak C-H...O contacts, have on the energy preference of the Phi(N) torsion angle.

Conformational preferences of the aglycon moiety in models and analogs of GlcNAc-Asn linkage: crystal structures and ab initio quantum chemical calculations of N-(beta-D-glycopyranosyl)haloacetamides.

The biological addition of oligosaccharide structures to asparagine residues of N-glycoproteins influences the properties and bioactivities of these macromolecules. The linkage region constituents, 2-acetamino-2-deoxy-beta-D-glucopyranose monosaccharide (GlcNAc) and L-asparagine amino acid (Asn), are conserved in the N-glycoproteins of all eukaryotes. In order to gain information about the structure and dynamics of glycosylated proteins, two chloroacetamido sugars, Glc betaNAcNHCOCH2Cl and Man betaNHCOCH2Cl, have been synthesized, and their crystal structures have been solved. Structural comparison with a series of other models and analogs gives insight about the influence of the N-acetyl group at position C2 on the conformation of the glycan-peptide linkage at C1. Interestingly, this N-acetyl group also influences the packing and network of hydrogen bonds with involvement in weak hydrogen bonds C-H...X that are of biological importance. DFT ab initio calculations performed on a series of models and analogs also confirm that the GlcNAc derivatives present different preferred conformation about the N-CO-CH2-X (chi2) torsion angle of the glycan-peptide linkage, when compared to other monosaccharide derivatives. The energy profiles that have been obtained will be useful for parametrization of molecular mechanics force-field. The conjunction of crystallographic and computational chemistry studies provides arguments for the structural effect of the N-acetyl group at C2 in establishing an extended conformation that presents the oligosaccharide away from the protein surface.