X-Ray Crystallographic Investigation of Fully Acetylated N-(2-Deoxy-2-Acetamido-β-D-Glucopyranosyl)Alkanamides as N-Glycoprotein Linkage Region Analogs

To understand the structural significance of the linkage region of N-glycoproteins, three title sugar amides have been prepared as analogs and their molecular assembly and crystal structures have been solved to explore the effect of acetyl protection and aglycon variation on the conformation, particularly of the N-glycosidic linkage. Comparative analysis of these structures with those of free sugar amides reported earlier showed that conformation of the amido aglycon moiety is not altered significantly by the masking of hydroxyl groups in the form of acetate. The bifurcated antiparallel pattern involving N-H center dot center dot center dot O and C-H center dot center dot center dot O hydrogen bonds, a hallmark of the N-glycoprotein models GlcNAc beta NHAc and GlcNAc beta Asn, is absent in all of the fully protected title alkanamides. The asymmetric unit of the tri-O-acetylated GIcNAc beta NHAc contains two different conformations, in one of which the double-pillared hydrogen bond network involving C1 and C2 acetamido groups is antiparallel, while it is parallel in the other. The co-occurrence of a molecular assembly motif- double-pillared parallel and antiparallel hydrogen bonding pattern-is hitherto unknown in the crystal structures of N-glycoprotein linkage region models and analogs.