Use of Circular Statistics To Model αMan-(1→2)-αMan and αMan-(1→3)-α/βMan O-Glycosidic Linkage Conformation in 13C-Labeled Disaccharides and High-Mannose Oligosaccharides

Abstract

A new experimental method, MA' AT analysis, has been applied to investigate the conformational properties of O-glycosidic linkages in several biologically important mannose-containing di- and oligosaccharides. Methyl α-d-mannopyranosyl-(1→2)-α-d-mannopyranoside (2), methyl α-d-mannopyranosyl-(1→3)-α-d-mannopyranoside (3), and methyl α-d-mannopyranosyl-(1→3)-β-d-mannopyranoside (4) were prepared with selective ¹³C-enrichment to enable the measurement of NMR scalar couplings across their internal O-glycosidic linkages. Density functional theory (DFT) was used to parameterize equations for J_CH and J_CC values in 2-4 that are sensitive to phi (ϕ) and psi (ψ). The experimental J-couplings and parameterized equations were treated using a circular statistics algorithm encoded in the MA' AT program. Conformations about ϕ and ψ treated using single-state von Mises models gave excellent fits to the ensembles of redundant J-couplings. Mean values and circular standard deviations (CSDs) for each linkage torsion angle ϕ (CSD) and ψ (CSD) in 2, -29° (25°) and 20° (22°); in 3, -36° (36°) and 8° (27°); in 4, -37° (34°) and 10° (26°); ϕ = H1'-C1'-O1'-CX and ψ = C1'-O1'-CX-HX (CX = aglycone carbon) were compared to histograms obtained from 1 μs aqueous molecular dynamics (MD) simulations and X-ray database statistical analysis. MA' AT-derived models of ψ were in very good agreement with the MD and X-ray data, but not those of ϕ, suggesting a need for force field revision. The effect of structural context on linkage conformation was also investigated in four selectively ¹³C-labeled homomannose tri- and tetrasaccharides using the MA' AT method. In the cases examined, context effects were found to be small.