N-Linked glycosylation is not only present in eukaryotes but also occurs in archaea and bacteria and is mainly characterized by the β-glucosylamine linkage to the asparagine (GlcNAcβAsn). Earlier crystallographic studies aimed at understanding the structural significance of the linkage region constituents revealed that N-glycosidic torsion, φN is influenced considerably by variation in the glycan part as compared to the aglycon moiety. The φN value observed for XylβNHAc deviated maximum as compared to that of the model compound, GlcNAcβNHAc. The present work was undertaken to assess the influence of ribose on the N-glycosidic torsions and molecular assembly. Several ribopyranosyl alkanamides have been synthesized and crystal structures of three of them have been solved. A comprehensive crystal structure analysis of ribosyl alkanamides along with xylosyl and arabinosyl alkanamides showed the wide range of deviations in their φN values as compared to the negligible deviation shown by hexopyranosyl alkanamides. This study revealed the importance of C5-hydroxymethyl group and hydroxyl group configurations at C2, C3, and C4 stereocentres in controlling the N-glycosidic torsions. © 2013 Elsevier Ltd. All rights reserved.

Manoharan Mathiselvam

Babu Varghese

Duraikkannu Loganathan

ANALOGS

Crystal structure analysis

Crystallographic studies

Hydroxyl groups

HYDROXYMETHYL GROUPS

LINKAGE REGION

MOLECULAR ASSEMBLY

N-LINKED GLYCOSYLATION

Amino acids

Crystal Structure

Methanol

X ray crystallography

Torsional stress

AGLYCONE

asparagine

glycan

glycoprotein

hydroxyl group

N (RIBOPYRANOSYL)ALKANAMIDE DERIVATIVE

unclassified drug

amide

aminosugar

glycoside

ribose

article

glycosylation

priority journal

stereochemistry

synthesis

Torsion

analogs and derivatives

chemical structure

chemistry

Stereoisomerism

Eukaryota

Amides

Amino sugars

Crystallography, X-Ray

glycoproteins

Glycosides

Models, Molecular

Molecular Structure

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

Novel glycolipids with thiourea- and urea-linkers have been synthesized as low-molecular-weight gelators by reacting glycosyl aminoacetamides with alkyl isothiocyanates and isocyanates. The influence of the linker groups on their self-assembly properties has been studied. A gelation study of the obtained neoglycolipids in various solvents showed that they are good hydrogelators. Urea-linked glycolipids showed better hydrogelating ability as compared to thiourea linked glycolipids. The influence of sugar head group and alkyl chain length on the glycolipid's self-assembly has also been studied. The fibrillar structures of the supramolecular hydrogels have been characterized by scanning electron microscopy (SEM). The thermal properties of the hydrogels formed by urea linked glycolipids have been studied by differential scanning calorimetry (DSC) and VT-NMR. Molecular packing has been studied by small angle (SAXS) and single crystal X-ray diffraction methods. © The Royal Society of Chemistry 2013.

RSC Advances

Synthesis and characterization of thiourea- and urea-linked glycolipids as low-molecular-weight hydrogelators

N-Glycoprotein linkage region constituents namely 2-deoxy-2-acetamido- β-d-glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all eukaryotes. Earlier crystallographic studies on the linkage region conformation revealed that among all the models and analogs of the N-glycoprotein linkage region, XylβNHAc showed maximum deviation in the φN value as compared to the value reported for the model compound, GlcNAcβNHAc. In order to understand the effect of another pentopyranose, viz., arabinose, on the N-glycosidic torsion angles and molecular assembly, three arabinopyranosyl alkanamides were synthesized and their X-ray crystal structures elucidated. A comparative analysis of the N-glycosidic torsion, φN of the three analogs revealed the greater rotational freedom around the C1-N1 bond as compared to the GlcNAc derivatives. Molecular assembly of propionamido and chloroacetamido derivatives is characterized by the presence of anti-parallel bilayers of the molecules. This unique molecular assembly is hitherto unknown in all other models and analogs of N-glycoprotein linkage region. This study reveals that N-glycosidic torsions are influenced by the glycan as well as molecular packing. © 2013 Elsevier Ltd. All rights reserved.

Synthesis and X-ray crystallographic investigation of N-(α-d- arabinopyranosyl)alkanamides as N-glycoprotein linkage region analogs

As part of our ongoing program aimed at understanding the structural significance of GlcNAcβAsn linkage conserved in all eukaryotic N-glycoproteins, the present study reports on the synthesis and X-ray crystal structures of N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)acetamide (Glc 3NAcβNHAc) and the corresponding propionamide (Glc 3NAcβNHPr). Comparative analysis of these structures with those of the corresponding GlcNAc (C2 acetamido) compounds showed that the bifurcated anti-parallel pattern involving N-H-O and C-H-O hydrogen bonds, the hallmark feature of the N-glycoprotein models, GlcNAcβNHAc and GlcNAcβAsn, is absent in both the C3 acetamido analogs. The extended (anti) conformation of the amido aglycon moiety as defined by X2 seen in the case of C2 acetamido derivative, GlcNAcβNHPr, turns into gauche for the C3 acetamido analog (Glc3NAcβNHPr). This observation is consistent with the earlier work on the critical role of the C2-NHAc group of GlcNAcβAsn in controlling ?2 at the linkage region of N-glycoproteins. © The Author(s) 2011.

Glycoconjugate Journal

Synthesis and X-ray crystallographic investigation of N-(3-deoxy-3- acetamido-β-D-glycopyranosyl)alkanamides as analogs of N-glycoprotein linkage region

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

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

Examination of the influence of C5-hydroxymethyl group and configurations of hydroxyl groups at C2, C3, and C4 stereocentres on the N-glycosidic torsion: Synthesis and X-ray crystallographic investigation of N-(d-ribopyranosyl) alkanamides as N-glycoprotein linkage region analogs

Journal	Carbohydrate Research
ISSN	00086215
Open Access	No