title: Conformational Populations of β-(1→4) O-Glycosidic Linkages Using Redundant NMR J-Couplings and Circular Statistics.
abstract: Twelve disaccharides containing β-(1→4) linkages and displaying systematic structural variations in the vicinity of these linkages were selectively labeled with13C to facilitate measurements of multiple NMR spin-spin (scalar; J) coupling constants (JCHand JCCvalues) across their O-glycosidic linkages. Ensembles of spin-couplings (2JCOC,3JCOCH,3JCOCC) sensitive to the two linkage torsion angles, phi (ϕ) and psi (ψ), were analyzed by using parametrized equations obtained from density functional theory (DFT) calculations, Fredholm theory, and circular statistics to calculate experiment-based rotamer populations for ϕ and ψ in each disaccharide. With the statistical program MA'AT, torsion angles ϕ and ψ were modeled as a single von Mises distribution, which yielded two parameters, the mean position and the circular standard deviation (CSD) for each angle. The NMR-derived rotamer populations were compared to those obtained from 1 μs aqueous molecular dynamics (MD) simulations and crystallographic database statistical analyses. Conformer populations obtained exclusively from the MA'AT treatment of redundant J-couplings were in very good agreement with those obtained from the MD simulations, providing evidence that conformational populations can be determined by NMR for mobile molecular elements such as O-glycosidic linkages with minimal input from theory. The approach also provides an experimental means to validate the conformational preferences predicted from MD simulations. The conformational behaviors of ϕ in the 12 disaccharides were very similar, but those of ψ varied significantly, allowing a classification of the 12 disaccharides based on preferred linkage conformation in solution.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Toby
authors.initials: T
authors.lastname: Turney
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Reagan
authors.initials: R
authors.lastname: Meredith
authors.affiliation: Omicron Biochemicals Inc. , South Bend, Indiana 46617-2701, United States.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Luke
authors.initials: L
authors.lastname: Sernau
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Wuhan University of Technology , Wuhan 430070, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
authors.affiliation: Radiation Laboratory, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Carmichael
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556-5670, United States.
authors.forename: Anthony S
authors.identifier: 0000-0001-6114-1446
authors.initials: AS
authors.lastname: Serianni
mesh_terms: D002236:Carbohydrate Conformation; D006027:Glycosides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D015233:Models, Statistical; D011789:Quantum Theory; D012015:Reference Standards
chemical_list: D006027:Glycosides