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Conformational flexibility and dynamics of two (1→6)-linked disaccharides related to an oligosaccharide epitope expressed on malignant tumour cells
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
2009 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 15, no 35, 8886-8894 p.Article in journal (Refereed) Published
Abstract [en]

The conformational flexibility and dynamics of two (1→6)-linked disaccharides that are related to the action of the glycosyl transferase GnT-V have been investigated. NMR NOE and T-ROE spectroscopy experiments, conformation-dependent coupling constants and molecular dynamics (MD) simulations were used in the analyses. To facilitate these studies, the compounds were synthesised as α-d-[6-13C]-Manp-OMe derivatives, which reduced the 1H NMR spectral overlap and facilitated the determination of two- and three-bond 1H,1H, 1H,13C and 13C,13C-coupling constants. The population distribution for the glycosidic ω torsion angle in α-d-Manp-(1→6)-α-d-Manp-OMe for gt/gg/tg was equal to 45:50:5, whereas in α-d-Manp-OMe it was determined to be 56:36:8. The dynamic model that was generated for β-d-GlcpNAc-(1→6)-α-d-Manp-OMe by MD simulations employing the PARM22/SU01 CHARMM-based force field was in very good agreement with experimental observations. β-d-GlcpNAc-(1→6)-α-d-Manp-OMe is described by an equilibrium of populated states in which the ϕ torsion angle has the exo-anomeric conformation, the ψ torsion angle an extended antiperiplanar conformation and the ω torsion angle a distribution of populations predominantly between the gauchetrans and the gauchegauche conformational states (i.e., gt/gg/tg) is equal to 60:35:5, respectively. The use of site-specific 13C labelling in these disaccharides leads to increased spectral dispersion, thereby making NMR spectroscopy based conformational analysis possible that otherwise might be difficult to attain.

Place, publisher, year, edition, pages
2009. Vol. 15, no 35, 8886-8894 p.
Keyword [en]
carbohydrates, enzymes, molecular dynamics, NMR spectroscopy, torsion angles
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-29504DOI: 10.1002/chem.200900507ISI: 000270045500030OAI: oai:DiVA.org:su-29504DiVA: diva2:233823
Available from: 2009-09-02 Created: 2009-09-02 Last updated: 2017-12-13Bibliographically approved
In thesis
1. NMR spectroscopy and MD simulations of carbohydrates
Open this publication in new window or tab >>NMR spectroscopy and MD simulations of carbohydrates
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Knowledge about the structure, conformation and dynamics of carbohydrates is important in our understanding of the way carbohydrates function in biological systems, for example in intermolecular signaling and recognition. This thesis is a summary of five papers studying these properties in carbohydrate-containing molecules with NMR spectroscopy and molecular dynamics simulations.

In paper I, the ring-conformations of the six-membered rings of two carbaiduronic analogs were investigated. These carbasugars could potentially be used as hydrolytically stable mimics of iduronic acid in drugs. The study showed that the equilibrium is entirely shifted towards the 4C1 conformation.

Paper II is an investigation of the conformational flexibility and dynamics of two (1→6)-linked disaccharides related to an oligosaccharide epitope expressed on malignant tumor cells.

In paper III, the conformational space of the glycosidic linkage of an alfa-(1→2) linked mannose disaccharide present in N- and O-linked glycoproteins, was studied. A maximum entropy analysis using different priors as background information was used and four new Karplus equations for 3JC,C and 3JC,H coupling constants, related to the glycosidic linkage, were presented.

Paper IV describes a structural elucidation of the exopolysaccharide (EPS) produced by Streptococcus thermophilus ST1, a major dairy starter used in yoghurt and cheese production. The EPS contains a hexasaccharide repeating unit of d-galactose and d-glucose residues, which is a new EPS structure of the S. thermophilus species.

In paper V, the dynamics of three generations of glycodendrimers were investigated by NMR diffusion and 13C NMR relaxation studies. Three different correlations times were identified, one global correlation time describing the rotation of the dendrimer as a whole, one local correlation time describing the reorientation of the C-H vectors, and one correlation time describing the pulsation of a dendrimer branch.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2011. 75 p.
Keyword
NMR specroscopy, MD simulations, carbohydrates
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:su:diva-61569 (URN)978-91-7447-348-3 (ISBN)
Public defence
2011-09-30, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Available from: 2011-09-08 Created: 2011-08-23 Last updated: 2011-08-23Bibliographically approved

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