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Synthesis and conformational analysis of carbasugar bioisosteres of alpha-L-iduronic acid and its methyl glycoside
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.
2010 (English)In: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 345, no 8, 984-993 p.Article in journal (Refereed) Published
Abstract [en]

The synthesis of two novel carbasugar analogues of α-l-iduronic acid is described in which the ring-oxygen is replaced by a methylene group. In analogy with the conformational equilibrium described for α-l-IdopA, the conformation of the carbasugars was investigated by 1H and 13C NMR spectroscopy. Hadamard transform NMR experiments were utilised for rapid acquisition of 1H,13C-HSQC spectra and efficient measurements of heteronuclear long-range coupling constants. Analysis of 1H NMR chemical shifts and JH,H coupling constants extracted by a total-lineshape fitting procedure in conjunction with JH,C coupling constants obtained by three different 2D NMR experiments, viz., 1H,13C-HSQC-HECADE, J-HMBC and IPAP-HSQC-TOCSY-HT, as well as effective proton–proton distances from 1D 1H,1H T-ROE and NOE experiments showed that the conformational equilibrium 4C12S5a1C4 is shifted towards 4C1 as the predominant or exclusive conformation. These carbasugar bioisosteres of α-l-iduronic acid do not as monomers show the inherent flexibility that is anticipated to be necessary for biological activity.

Place, publisher, year, edition, pages
2010. Vol. 345, no 8, 984-993 p.
Keyword [en]
Heparin, Conformational equilibrium, NMR, Molecular modelling
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-59758DOI: 10.1016/j.carres.2010.03.002ISI: 000278747700001OAI: oai:DiVA.org:su-59758DiVA: diva2:430758
Available from: 2011-07-12 Created: 2011-07-12 Last updated: 2017-12-11Bibliographically 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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