The torsion angle around the N-glycoprotein linkage region (GlcNAc-Asn) is an important factor for presenting sugar on the cell surface which is crucial for many biological processes. Earlier studies using model and analogs showed that this important torsion angle is greatly influenced by substitutions in the sugar part. In the present work, uronic acid alkanamides and triazole derivatives have been designed and synthesized as newer analogs of N-glycoprotein linkage region to understand the influence of the carboxylic group on linkage region torsion as well as on molecular packing. Crystal structure of N-(β-d-galacturonopyranosyl)acetamide is solved with the space group of P22121. Comparison of the torsion angle and molecular packing of this compound with N-(β-d-galactopyranosyl)acetamide showed that changing the C6-hydoxymethyl group to the carboxylic acid group has minimum influence on the N-glycosidic torsion angle, ΦN and significant influence on the molecular packing. © 2013 Elsevier Ltd. All rights reserved.

Manoharan Mathiselvam

Duraikkannu Loganathan

Babu Varghese

Carboxylic acids

Cell membranes

glycoproteins

Self assembly

X ray crystallography

Biological process

CARBOXYLIC ACID GROUPS

Carboxylic group

LINKAGE REGION

MOLECULAR PACKINGS

N-GLYCOPROTEIN

TRIAZOLE DERIVATIVES

URONIC ACIDS

Torsional stress

1 (BETA D GLYCURONOPYRANOSYL) 4 PHENYL[1,2,3]TRIAZOLE

carboxylic acid

glycoprotein

N (BETA D GLYCURONOPYRANOSYL)ALKANAMIDE

N GLYCOPROTEIN

triazole derivative

unclassified drug

URONIC ACID

article

chemical structure

Crystal Structure

priority journal

synthesis

N-GLYCOSIDIC TORSION

X-ray crystallography

Amides

Biomimetic Materials

Chemistry Techniques, Synthetic

Crystallography, X-Ray

Glycosides

Models, Molecular

protein conformation

Triazoles

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Carbohydrate Research

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, N, 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 N 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. © 2013 Springer Science+Business Media New York.

Glycoconjugate Journal

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

Synthesis of N-(β-d-glycuronopyranosyl)alkanamides and 1-(β-d-glycuronopyranosyl)-4-phenyl-[1,2,3]-triazoles as N-glycoprotein linkage region analogs: Examination of the effect of C5 substituent on the N-glycosidic torsion (ΦN) based on X-ray crystallography

GlcNAcβAsn 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 β-1-N-acetamido- and propionamido derivatives of monosaccharides has earlier shown that the N-glycosidic torsion, ΦN, 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 ΦN, several models and analogs with gluco and manno configuration have been studied in the present work by computational chemistry. The crystal structure of XylβNHPr 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 ΦN torsion angle. © 2008 Elsevier Ltd. All rights reserved.

Examination of the effect of structural variation on the N-glycosidic torsion (ΦN) among N-(β-d-glycopyranosyl)acetamido and propionamido derivatives of monosaccharides based on crystallography and quantum chemical calculations

A general and expedient method based on a click reaction has been developed for the synthesis of novel glycolipids. The Cu(I) catalyzed [3+2] cycloaddition of several fully acetylated β- as well as α-d-glycopyranosyl azides, including the 1,6-diazide derived from d-glucose, with long chain alkyl propargyl ethers gave the respective 1,4-substituted 1,2,3-triazole derivatives in good yields. Treatment of fully acetylated N-(β-glycopyranosyl)azidoacetamides under similar conditions with alkyl propargyl ethers afforded the 1,2,3-triazolylacetamido derivatives in fairly good yields. Zemplen de-O-acetylation of all the fully acetylated derivatives furnished the free glycolipids in quantitative yields. © 2008 Elsevier Ltd. All rights reserved.

Tetrahedron Letters

Synthesis of novel glycolipids derived from glycopyranosyl azides and N-(β-glycopyranosyl)azidoacetamides

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-β-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, GlcβNAcNHCOCH2Cl and ManβNHCOCH2Cl, 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-CH 2-X (χ2) 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. © 2008 American Chemical Society.

Journal of the American Chemical Society

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

Elucidation of the intra- and intermolecular carbohydrate-protein interactions would greatly contribute toward obtaining a better understanding of the structure-function correlations of the protein-linked glycans. The weak interactions involving C-H...O have recently been attracting immense attention in the domain of biomolecular recognition. However, there has been no report so far on the occurrence of C-H...O hydrogen bonds in the crystal structures of models and analogs of N-glycoproteins. We present herein an analysis of C-H...O interactions in the crystal structures of all N-glycoprotein linkage region models and analogs. The study reveals a cooperative network of bifurcated hydrogen bonds consisting of N-H...O and C-H...O interactions seen uniquely for the models. The cooperative network consists of two antiparallel chains of bifurcated hydrogen bonds, one involving N1-H, C2′-H and O1′ of the aglycon moiety and the other involving N2-H, C1-H and O1″ of the sugar. Such bifurcated hydrogen bonds between the core glycan and protein are likely to play an important role in the folding and stabilization of proteins. © 2006 Oxford University Press.

Fulltext

Glycobiology

Observation of a unique pattern of bifurcated hydrogen bonds in the crystal structures of the N-glycoprotein linkage region models

Journal	Data powered by TypesetCarbohydrate Research
Publisher	Data powered by TypesetElsevier Ltd
ISSN	00086215
Open Access	No