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- Engström, Olof, 1983-
(författare)
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Exploring the Molecular Behavior of Carbohydrates by NMR Spectroscopy : Shapes, motions and interactions
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carbohydrates are essential biomolecules that decorate cell membranes and proteins in organisms. They are important both as structural elements and as identification markers. Many biological and pathogenic processes rely on the identification of carbohydrates by proteins, thereby making them attractive as molecular blueprints for drugs. This thesis describes how NMR spectroscopy can be utilized to study carbohydrates in solution at a molecular level. This versatile technique facilitates for investigations of (i) shapes, (ii) motions and (iii) interactions.A conformational study of an E. coli O-antigen was performed by calculating atomic distances from NMR NOESY experiments. The acquired data was utilized to validate MD simulations of the LPS embedded in a membrane. The agreement between experimental and calculated data was good and deviations were proven to arise from spin-diffusion. In another study presented herein, both the conformation and the dynamic behavior of amide side-chains linked to derivatives of D-Fucp3N, a sugar found in the O-antigen of bacteria, were investigated. J-couplings facilitated a conformational analysis and 13C saturation transfer NMR experiments were utilized to measure rate constants of amide cis-trans isomerizations.13C NMR relaxation and 1H PFG diffusion measurements were carried out to explore and describe the molecular motion of mannofullerenes. The dominating motions of the mannofullerene spectral density were found to be related to pulsating motions of the linkers rather than global rotational diffusion. The promising inhibition of Ebola viruses identified for a larger mannofullerene can thus be explained by an efficient rebinding mechanism that arises from the observed flexibility in the linker.Molecular interactions between sugars and caffeine in water were studied by monitoring chemical shift displacements in titrations. The magnitude of the chemical shift displacements indicate that the binding occurs by a face to face stacking of the aromatic plane of caffeine to the ring plane of the sugar, and that the interaction is at least partly driven by solvation effects. Also, the binding of a Shigella flexneri serotype Y octasaccharide to a bacteriophage Sf6 tail spike protein was investigated. This interaction was studied by 1H STD NMR and trNOESY experiments. A quantitative analysis of the STD data was performed employing a newly developed method, CORCEMA-ST-CSD, that is able to simulate STD data more accurately since the line broadening of protein resonances are accounted for in the calculations.
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| 2. |
- Olsson, Ulrika, et al.
(författare)
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Conformational analysis of β-linked glucobiosides based on hetero- and homonuclear couplings across the glycosidic linkage
- 2008
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 112:14, s. 4447-4453
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Tidskriftsartikel (refereegranskat)abstract
- Four β-linked glucobioses selectively 13C labeled at C1‘ or C2‘ have been prepared. The inter-residue coupling constants, JCH, and JCC, have been determined and related to the solution conformations of the disaccharides using Karplus-type relationships. Relying only on the experimental coupling constants, glycosidic linkage conformation in methyl α-sophoroside (methyl 2-O-β-d-glucopyranosyl-α-d-glucopyranoside), methyl α-laminarabioside (methyl 3-O-β-d-glucopyranosyl-α-d-glucopyranoside), and methyl α-cellobioside (methyl 4-O-β-d-glucopyranosyl-α-d-glucopyranoside) were found to be close to those observed in the solid state (39° < H < 41°, −24° < ψH < −36°). The laminarabioside and cellobioside were found to have conformations that accommodate an intramolecular hydrogen bond to O5‘ that is observed in the solid state. In all compounds, the exocyclic hydroxymethyl groups retain a conformation close to that observed in unsubstituted glucose (gt/gg 1:1). Methyl α-gentiobioside (methyl 6-O-β-d-glucopyranosyl-α-d-glucopyranoside) shows greater flexibility at the ψ-torsion than the other disaccharides, but the population distribution around the C5−C6 bond is essentially unaffected by substitution. None of the O2‘ hydroxyl groups of the β-d-glucopyranosyl residues in any of the disaccharides appear to be involved in inter-residue hydrogen bonding since 1JCH, 1JCC, and 2JCH values sensitive to C2‘−O2‘ rotamer distribution remain close to those observed in methyl β-d-glucopyranoside.
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