Synthesis and X-ray crystallographic investigation of N-(β-d-glycosyl)butanamides derived from GlcNAc and chitobiose as analogs of the conserved chitobiosylasparagine linkage of N-glycoproteins

Abstract

The linkage region, GlcNAcβAsn, is conserved in all eukaryotic N-glycoproteins. As a logical extension of a research endeavor aimed at understanding the structural significance of GlcNAc and Asn as the linkage region constituents, the newer analogs GlcNAcβNHBu and (GlcNAcβ(1–4)GlcNAc)alkanamides have been synthesized to assess the influence of aglycon as well as additional GlcNAc on the linkage region. X-ray crystallographic analysis of the GlcNAcβNHBu and (GlcNAcβ(1–4)GlcNAc)βNHBu is described. Comparative analysis of these structures with those of reported models and analogs shows that the deviation in N-glycosidic torsion, ϕN among the GlcNAc alkanamides is negligible (<2°) whereas (GlcNAcβ(1–4)GlcNAc)βNHBu deviates by ∼15° as compared to GlcNAcβNHBu. Under the influence of the molecular packing, the conformation around the C1′–C2′ bond deviates from anti to gauche in (GlcNAcβ(1–4)GlcNAcβNHBu. Interestingly, C2-acetamido group in (GlcNAcβ(1–4)GlcNAc)NHBu orients differently as compared to GlcNAc alkanamides and this orientation was found to be almost similar to β-N,N′-diacetylchitobiose trihydrate. The bifurcated anti-parallel pattern involving N–H⋯O and C–H⋯O hydrogen bonds, a hallmark feature of the N-glycoprotein models, GlcNAcβNHAc and GlcNAcβAsn, is absent in both the title alkanamides. This is the first report on the crystal structure analysis of chitobiosyl alkanamide as analog of the N-glycoprotein linkage region, (GlcNAcβ(1–4)GlcNAc)βAsn.