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

Abstract

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.