Effect of distal sugars and interglycosidic linkage on the N-glycoprotein linkage region conformation: synthesis and X-Ray crystallographic investigation of β-1-N-alkanamide derivatives of cellobiose and maltose as disaccharide analogs of the conserved chitobiosylasparagine linkage

Abstract

The linkage region constituents, 2-deoxy-2-acetamido-β-D-glucopyranose (GlcNAc) and L-asparagine (Asn) are conserved in the N-glycoproteins of all eukaryotes. Elucidation of the structure and conformation of the linkage region of glycoproteins is important to understand the presentation and dynamics of the carbohydrate chain at the protein/cell surface. Earlier crystallographic studies using monosaccharide models and analogs of N-glycoprotein linkage region have shown that the N-glycosidic torsion, ϕN, is more influenced by the structural variation in the sugar part than that of the aglycon moiety. To access the influence of distal sugar as well as interglycosidic linkage (α or β) on the N-glycosidic torsion angles, cellobiosyl and maltosyl alkanamides have been synthesized and structural features of seven of these analogs have been characterized by X-ray crystallography. Comparative analysis of the seven disaccharide analogs with the reported monosaccharide analogs showed that the ϕN value of cellobiosyl analogs deviate ~9° with respect to GlcβNHAc. In the case of maltosyl analogs, deviation is more than 18°. These deviations indicate that the N-glycosidic torsion is influenced by addition of distal sugar as well as with respect to inter glycosidic linkage (α or β); it is less influenced by changes occurring at the aglycon. The χ₂ value of alkanamide derived from glucose, cellobiose and maltose exhibit a large range of variations (from 1.6° to -109.9°). This large span of χ₂ value suggests the greater degree of rotational freedom around C1'-C2' bond which is restricted in GlcNAc alkanamides. The present finding explicitly proved the importance of molecular architecture in the N-glycoproteins linkage region to maintain the linearity, planarity and rigidity. These factors are necessary for N-glycan to serve role in inter- as well as intramolecular carbohydrate-protein interactions.

Effect of distal sugar and interglycosidic linkage of disaccharides on the activity of proline rich antimicrobial glycopeptides

“…These results suggest that the effect of interglycosidic linkage of disaccharide attached to threonine on the antibacterial activity is more pronounced than the nature of distal sugar of glycosylated analogs of these proline‐rich AMPs. Different configuration of interglycosidic linkages ( α or β ) are known to influence the N ‐glycosidic torsion angle at different extents in case of N ‐linked glycosides. It has been reported that small changes in carbohydrate composition are sufficient to induce conformational changes in the peptide .…”

Gas chromatography‑time of flight/mass spectrometry‑based metabonomics of changes in the urinary metabolic profile in osteoarthritic rats

“…Maltose is a primary disaccharide in the human diet, formed from two units of glucose joined with an alpha linkage. It is the second member of an important biochemical series of glucose chains ( 43 ). In the present study, the contents of shikimic acid, 1,4-dihydroxy-naphthoic acid, N-acetyl-D-galactosamine, trehalose, gentiobiose and xylose were decreased, while the maltose content was increased in the KOA group when compared with the control group, which may be related to the inhibition of the glycolysis and pentose phosphate pathways and increased blood glucose levels.…”