title: Exploring the effect of bioisosteric replacement of carboxamide by a sulfonamide moiety on N-glycosidic torsions and molecular assembly: synthesis and X-ray crystallographic investigation of N-(β-D-glycosyl)sulfonamides as N-glycoprotein linkage region analogues.
abstract: N-Glycoprotein linkage region constituents, 2-acetamido-2-deoxy-β-D-glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the eukaryotes. To gain a better understanding for nature's choice of GlcNAcβAsn as linkage region constituents and inter- and intramolecular carbohydrate-protein interactions, a detailed systemic structural study of the linkage region conformation is essential. Earlier crystallographic studies of several N-(β-glycopyranosyl)alkanamides showed that N-glycosidic torsion, φN , is influenced to a larger extent by structural variation in the sugar part than that of the aglycon moiety. To explore the effect of the bioisosteric replacement of a carboxamide group by a sulfonamide moiety on the N-glycosidic torsions as well as on molecular assembly, several glycosyl methanesulfonamides and glycosyl chloromethanesulfonamides were synthesized as analogues of the N-glycoprotein linkage region, and crystal structures of seven of these compounds have been solved. A comparative analysis of this series of crystal structures as well as with those of the corresponding alkanamido derivatives revealed that N-glycosidic torsion, φN, does not alter significantly. Methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc display a different aglycon conformation compared to other sulfonamido analogues. This may be due to the cumulative effect of the direct hydrogen bonding between N1 and O1' and C-H···O interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the linkage sugar.
authors: Department of Chemistry, Indian Institute of Technology Madras, Chennai - 600036 (India), Fax: (+91) 44-22574202. amrisriv9@gmail.com.
authors: Amrita
authors: A
authors: Srivastava
authors: Babu
authors: B
authors: Varghese
authors: Duraikkannu
authors: D
authors: Loganathan
mesh_terms: D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D006023:Glycoproteins; D013449:Sulfonamides
keywords: CH⋅⋅⋅O interactions; N-glycoproteins; X-ray diffraction; proteins; sulfonamides