Change search
Refine search result
1 - 17 of 17
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Blasco, Pilar
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Patel, Dhilon S.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Im, Wonpil
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Conformational Dynamics of the Lipopolysaccharide from Escherichia coli O91 Revealed by Nuclear Magnetic Resonance Spectroscopy and Molecular Simulations2017In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 56, no 29, p. 3826-3839Article in journal (Refereed)
    Abstract [en]

    The outer leaflet of the outer membrane in Gram-negative bacteria contains lipopolysaccharides (LPS) as a major component, and the outer membrane provides a physical barrier and protection against hostile environments. The enterohemorrhagic Escherichia coli of serogroup O91 has an O-antigen polysaccharide (PS) with five sugar residues in the repeating unit (RU), and the herein studied O-antigen PS contains similar to 10 RUs. H-1-C-13 HSQC-NOESY experiments on a 1-C-13-labeled PS were employed to deduce H-1-H-1 cross-relaxation rates and transglycosidic (3)J(CH) related to the psi torsional angles were obtained by H-1-H-1 NOESY experiments. Dynamical parameters were calculated from the molecular dynamics (MD) simulations of the PS in solution and compared to those from C-13 nuclear magnetic resonance (NMR) relaxation studies. Importantly, the MD simulations can reproduce the dynamical behavior of internal correlation times along the PS chain. Two-dimensional free energy surfaces of glycosidic torsion angles delineate the conformational space available to the O-antigen. Although similar with respect to populated states in solution, the O-antigen in LPS bilayers has more extended chains as a result of spatial limitations due to close packing. Calcium ions are highly abundant in the phosphate-containing core region mediating LPS LPS association that is crucial for maintaining bilayer integrity, and the negatively charged O-antigen promotes a high concentration of counterbalancing potassium ions. The ensemble of structures present for the PS in solution is captured by the NMR experiments, and the similarities between the O-antigen on its own and as a constituent of the full LPS in a bilayer environment make it possible to realistically describe the LPS conformation and dynamics from the MD simulations.

  • 2.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Carbohydrate dynamics and interactions studied by NMR spectroscopy2013Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The combination of NMR spectroscopy and molecular dynamics (MD) simulations are powerful tools in the studying of bioorganic molecules in solution. In this thesis two such studies are presented with focus on the NMR aspect. The caffeine association to sugars (D-glucose and sucrose) was investigated by NMR titrations and NOESY experiments in paper I. The observations from the NMR experiments confirmed MD simulations showing that the binding occurs by a face-to-face interaction between the aromatic surface of the caffeine and axial protons of the sugar ring. Different sugar molecules and residues have different preferences regarding which side of the sugar ring that are involved in the binding. The sucrose residues bind with only one ring face each whereas β-D-glucopyranose has two sides of similar binding probability and the α-D-glucopyranose has something in between. The MD simulations showed that the driving force of the binding is partly driven by hydration effects that favor the enthalpy of the system. A new approach to calculate NMR relaxation parameters (that is dependent on molecular motions) from computational simulations is presented in paper II. Each sugar residue is assumed to be a rigid unit connected by flexible joints in the approach, thus the name diffusive chain model (DCM). The simplified model together with a stochastic simulation approach lowers the computational cost which makes it possible to acquire long enough trajectories to the calculations of spin relaxation parameters. Two case studies with slightly different methodologies are presented. In one of them, spin relaxation parameters are reproduced for the human milk oligosaccharide LNF-1 in a feasible way by the use of Brownian dynamics.

  • 3.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Exploring the Molecular Behavior of Carbohydrates by NMR Spectroscopy: Shapes, motions and interactions2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

  • 4.
    Engström, Olof
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mobarak, Hani
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ståhle, Jonas
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Conformational Dynamics and Exchange Kinetics of N-Formyl and N-Acetyl Groups Substituting 3-Amino-3,6-dideoxy-alpha-D-galactopyranose, a Sugar Found in Bacterial O-Antigen Polysaccharides2017In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 121, no 41, p. 9487-9497Article in journal (Refereed)
    Abstract [en]

    Three dimensional shape and conformation of. carbohydrates are important factors in molecular recognition events and the N-acetyl group of a monosaccharide residue can function as a conformational gatekeeper whereby it influences the overall shape of the oligosaccharide. NMR spectroscopy and quantum mechanics (QM) calculations are used herein to investigate both the conformational preferences and the dynamic behavior of N-acetyl and N-formyl substituents of 3-amino-3,6-dideoxy-alpha-D-galactopyranose, a sugar and substitution pattern found in bacterial O-antigen polysaccharides. QM calculations suggest that the amide oxygen can be involved in hydrogen bonding with the axial OH4 group primarily but also with the equatorial OH2 group. However, an NMR J coupling analysis indicates that the 01 torsion angle, adjacent to the sugar ring, prefers an ap conformation where conformations <180 degrees also are accessible, but does not allow for intramolecular hydrogen bonding. In the formyl-substituted compound (4)J(HH) coupling constants to the exo-cyclic group were detected and analyzed. A van't Hoff analysis revealed that the trans conformation at the amide bond is favored by Delta G degrees approximate to - 0.8 kcal.mol(-1) in the formyl-containing compound and with Delta G degrees approximate to -2.5 kcal.mol(-1) when the N-acetyl group is the substituent. In both cases the enthalpic term dominates to the free energy, irrespective of water or DMSO as solvent, with only a small contribution from the entropic term. The cis-trans isomerization of the theta(2) torsion angle, centered at the amide bond, was also investigated by employing H-1 NMR line shape analysis and C-13 NMR saturation transfer experiments. The extracted transition rate constants were utilized to calculate transition energy barriers that were found to be about 20 kcal.mol(-1) in both DMSO-d(6) and D2O. Enthalpy had a higher contribution to the energy barriers in DMSO-d(6) compared to in D2O, where entropy compensated for the loss of enthalpy.

  • 5.
    Engström, Olof
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Muñoz, Antonio
    Illescas, Beatriz M.
    Martin, Nazario
    Ribeiro-Viana, Renato
    Rojo, Javier
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Investigation of glycofullerene dynamics by NMR spectroscopy2015In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, no 32, p. 8750-8755Article in journal (Refereed)
    Abstract [en]

    Glycofullerenes, in which carbohydrate molecules are attached via a linker to a [60]fullerene core, facilitate spherical presentation of glyco-based epitopes. We herein investigate the dynamics of two glycofullerenes, having 12 and 36 mannose residues at their periphery, by NMR translational diffusion and quantitative C-13 relaxation studies employing a model-free approach for their interpretation. The sugar residues are shown to be highly flexible entities with S-2 < 0.2 in both compounds. Notably, the larger glycofullerene with longer linkers shows faster internal dynamics and higher flexibility than its smaller counterpart. The dynamics and flexibility as well as the slower translational diffusion of the larger glycofullerene, thereby favoring rebinding to a receptor, may together with its spatial extension explain why it is better than the smaller one at blocking the DC-SIGN receptor and inhibiting the infection by pseudotyped Ebola virus particles.

  • 6. Kang, Yu
    et al.
    Gohlke, Ulrich
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Hamark, Christoffer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Scheidt, Tom
    Heinemann, Udo
    Max-Delbrück-Centrum für Molekulare Medizin.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lipowski, Reinhard
    Santer, Mark
    Barbirz, Stefanie
    Probing the conformational space of Shigella flexneri O‑antigen bound to the tailspike protein of bacteriophage Sf6 by X-ray crystallography, NMR, and Molecular DynamicsManuscript (preprint) (Other academic)
  • 7. Kang, Yu
    et al.
    Gohlke, Ulrich
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Hamark, Christoffer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Scheidt, Tom
    Kunstrnann, Sonja
    Heinemann, Udo
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Santer, Mark
    Barbirz, Stefanie
    Bacteriophage Tailspikes and Bacterial O-Antigens as a Model System to Study Weak-Affinity Protein-Polysaccharide Interactions2016In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 138, no 29, p. 9109-9118Article in journal (Refereed)
    Abstract [en]

    Understanding interactions of bacterial surface polysaccharides with receptor protein scaffolds is important for the development of antibiotic therapies. The corresponding protein recognition domains frequently form low-affinity complexes with polysaccharides that are difficult to address with experimental techniques due to the conformational flexibility of the polysaccharide. In this work, we studied the tailspike protein (TSP) of the bacteriophage Sf6. Sf6TSP binds and hydrolyzes the high-rhamnose, serotype Y O-antigen polysaccharide of the Gram-negative bacterium Shigella flexneri (S. flexneri) as a first step of bacteriophage infection. Spectroscopic analyses and enzymatic cleavage assays confirmed that Sf6TSP binds long stretches of this polysaccharide. Crystal structure analysis and saturation transfer difference (STD) NMR spectroscopy using an enhanced method to interpret the data permitted the detailed description of affinity contributions and flexibility in an Sf6TSP-octasaccharide complex. Dodecasaccharide fragments corresponding to three repeating units of the O-antigen in complex with Sf6TSP were studied computationally by molecular dynamics simulations. They showed that distortion away from the low-energy solution conformation found in the octasaccharide complex is necessary for ligand binding. This is in agreement with a weak-affinity functional polysaccharide protein contact that facilitates correct placement and thus hydrolysis of the polysaccharide close to the catalytic residues. Our simulations stress that the flexibility of glycan epitopes together with a small number of specific protein contacts provide the driving force for Sf6TSP-polysaccharide complex formation in an overall weak-affinity interaction system.

  • 8.
    Kapla, Jon
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Stevensson, Baltzar
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Wohlert, Jakob
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Maliniak, Arnold
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Molecular dynamics simulations and NMR spectroscopy studies of trehalose-lipid bilayer systems2015In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 17, no 34, p. 22438-22447Article in journal (Refereed)
    Abstract [en]

    The disaccharide trehalose (TRH) strongly affects the physical properties of lipid bilayers. We investigate interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH using NMR spectroscopy and molecular dynamics (MD) computer simulations. We compare dipolar couplings derived from DMPC/TRH trajectories with those determined (i) experimentally in TRH using conventional high-resolution NMR in a weakly ordered solvent (bicelles), and (ii) by solid-state NMR in multilamellar vesicles (MLV) formed by DMPC. Analysis of the experimental and MD-derived couplings in DMPC indicated that the force field used in the simulations reasonably well describes the experimental results with the exception for the glycerol fragment that exhibits significant deviations. The signs of dipolar couplings, not available from the experiments on highly ordered systems, were determined from the trajectory analysis. The crucial step in the analysis of residual dipolar couplings (RDCs) in TRH determined in a bicelle-environment was access to the conformational distributions derived from the MD trajectory. Furthermore, the conformational behavior of TRH, investigated by J-couplings, in the ordered and isotropic phases is essentially identical, indicating that the general assumptions in the analyses of RDCs are well founded.

  • 9.
    Kapla, Jon
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Wohlert, Jakob
    Stevensson, Baltzar
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Maliniak, Arnold
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Molecular Dynamics Simulations of Membrane-Sugar Interactions2013In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 22, p. 6667-6673Article in journal (Refereed)
    Abstract [en]

    It is well documented that disaccharides in general and trehalose (TRH) in particular strongly affect physical properties and functionality of lipid bilayers. We investigate interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH by means of molecular dynamics (MD) computer simulations. Ten different TRH concentrations were studied in the range W-TRH = 0-0.20 (w/w). The potential of mean force (PMF) for DMPC bilayer TRH interactions was determined using two different force fields, and was subsequently used in a simple analytical model for description of sugar binding at the membrane interface. The MD results were in good agreement with the predictions of the model. The net affinities of TRH for the DMPC bilayer derived from the model and MD simulations were compared with experimental results. The area per lipid increases and the membrane becomes thinner with increased TRH concentration, which is interpreted as an intercalation effect of the TRH molecules into the polar part of the lipids, resulting in conformational changes in the chains. These results are consistent with recent experimental observations. The compressibility modulus related to the fluctuations of the membrane increases dramatically with increased TRH concentration, which indicates higher order and rigidity of the bilayer. This is also reflected in a decrease (by a factor of 15) of the lateral diffusion of the lipids. We interpret these observations as a formation of a glassy state at the interface of the membrane, which has been suggested in the literature as a hypothesis for the membrane sugar interactions.

  • 10. Kotsyubynskyy, Dmytro
    et al.
    Zerbetto, Mirco
    Šoltésová, Mária
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Charles University Prague .
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pendrill, Robert
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kowalewski, Josef
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Polimeno, Antonin
    Stochastic Modeling of Flexible Biomolecules Applied to NMR Relaxation: 2. Interpretation of Complex Dynamics in Linear Oligosaccharides2012In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 50, p. 14541-14555Article in journal (Refereed)
    Abstract [en]

    A computational stochastic approach is applied to the description of flexible molecules. By combining (i) molecular dynamics simulations, (ii) hydrodynamics approaches, and (iii) a multidimensional diffusive description for internal and global dynamics, it is possible to build an efficient integrated approach to the interpretation of relaxation processes in flexible systems. In particular, the model is applied to the interpretation of nuclear magnetic relaxation measurements of linear oligosaccharides, namely a mannose-containing trisaccharide and the pentasaccharide LNF-1. Experimental data are reproduced with sufficient accuracy without free model parameters.

  • 11.
    Mobarak, Hani
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of methyl 3-amino-3,6-dideoxy-alpha-d-galactopyranoside carrying different amide substituents2013In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 3, no 45, p. 23090-23097Article in journal (Refereed)
    Abstract [en]

    Bacterial polysaccharides may contain rare sugars of different stereochemistry and diverse functional groups; the repertoire can be further extended by varying the exocyclic substituents. Synthesis of four monosaccharides is described utilizing a suitably protected key intermediate obtained by regioselective acetal ring-opening reduction, dexoygenation at C6, alcohol oxidation at C3 followed by formation of an oxime, which was stereoselectively reduced by samarium diiodide to give a 3-amino-derivative having the desired galacto-configuration. Subsequent functionalization was performed resulting in one to four carbon atoms in the amide substituent.

  • 12.
    Muheim, Claudio
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bakali, Amin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Wieslander, Åke
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Daley, Daniel O.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Identification of a Fragment-Based Scaffold that Inhibits the Glycosyltransferase WaaG from Escherichia coli2016In: Antibiotics, ISSN 0066-4774, E-ISSN 2079-6382, Vol. 5, no 1Article in journal (Refereed)
    Abstract [en]

    WaaG is a glycosyltransferase that is involved in the biosynthesis of lipopolysaccharide in Gram-negative bacteria. Inhibitors of WaaG are highly sought after as they could be used to inhibit the biosynthesis of the core region of lipopolysaccharide, which would improve the uptake of antibiotics. Herein, we establish an activity assay for WaaG using C-14-labeled UDP-glucose and LPS purified from a increment waaG strain of Escherichia coli. We noted that addition of the lipids phosphatidylglycerol (PG) and cardiolipin (CL), as well as the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) increased activity. We then use the assay to determine if three molecular scaffolds, which bind to WaaG, could inhibit its activity in vitro. We show that 4-(2-amino-1,3-thiazol-4-yl)phenol inhibits WaaG (IC50 1.0 mM), but that the other scaffolds do not. This study represents an important step towards an inhibitor of WaaG by fragment-based lead discovery.

  • 13.
    Pendrill, Robert
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Volpato, Andrea
    Zerbetto, Mirco
    Polimeno, Antonino
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Flexibility at a glycosidic linkage revealed by molecular dynamics, stochastic modeling, and 13C NMR spin relaxation: conformational preferences of alpha-L-Rhap-alpha-(1 -> 2)-alpha-L-Rhap-OMe in water and dimethyl sulfoxide solutions2016In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 18, no 4, p. 3086-3096Article in journal (Refereed)
    Abstract [en]

    The monosaccharide L-rhamnose is common in bacterial polysaccharides and the disaccharide alpha-L-Rhap-alpha-(1 -> 2)-alpha-L-Rhap-OMe represents a structural model for a part of Shigella flexneri O-antigen polysaccharides. Utilization of [1'-C-13]-site-specific labeling in the anomeric position at the glycosidic linkage between the two sugar residues facilitated the determination of transglycosidic NMR (3)J(CH) and (3)J(CC) coupling constants. Based on these spin-spin couplings the major state and the conformational distribution could be determined with respect to the psi torsion angle, which changed between water and dimethyl sulfoxide (DMSO) as solvents, a finding mirrored by molecular dynamics (MD) simulations with explicit solvent molecules. The C-13 NMR spin relaxation parameters T-1, T-2, and heteronuclear NOE of the probe were measured for the disaccharide in DMSO-d(6) at two magnetic field strengths, with standard deviations <= 1%. The combination of MD simulation and a stochastic description based on the diffusive chain model resulted in excellent agreement between calculated and experimentally observed C-13 relaxation parameters, with an average error of <2%. The coupling between the global reorientation of the molecule and the local motion of the spin probe is deemed essential if reproduction of NMR relaxation parameters should succeed, since decoupling of the two modes of motion results in significantly worse agreement. Calculation of C-13 relaxation parameters based on the correlation functions obtained directly from the MD simulation of the solute molecule in DMSO as solvent showed satisfactory agreement with errors on the order of 10% or less.

  • 14.
    Rönnols, Jerk
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Schnupf, Udo
    Säwén, Elin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Brady, John W.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Inter-residual Hydrogen Bonding in Carbohydrates Unraveled by NMR Spectroscopy and Molecular Dynamics Simulations2019In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 20, p. 2519-2528Article in journal (Refereed)
    Abstract [en]

    Carbohydrates, also known as glycans in biological systems, are omnipresent in nature where they as glycoconjugates occur as oligo- and polysaccharides linked to lipids and proteins. Their three-dimensional structure is defined by two or three torsion angles at each glycosidic linkage. In addition, transglycosidic hydrogen bonding between sugar residues may be important. Herein we investigate the presence of these inter-residue interactions by NMR spectroscopy in D2O/[D-6]DMSO (70:30) or D2O and by molecular dynamics (MD) simulations with explicit water as solvent for disaccharides with structural elements alpha-d-Manp-(1 -> 2)-d-Manp, beta-d-GlcpNAc-(1 -> 2)-d-Manp, and alpha-d-Glcp-(1 -> 4)-beta-d-Glcp, all of which have been suggested to exhibit inter-residue hydrogen bonding. For the disaccharide beta-d-GlcpNAc-(1 -> 2)-beta-d-Manp-OMe, the large extent of O5 '...HO3 hydrogen bonding as seen from the MD simulation is implicitly supported by the H-1 NMR chemical shift and (3)J(HO3,H3) value of the hydroxy proton. In the case of alpha-d-Glcp-(1 -> 4)-beta-d-Glcp-OMe, the existence of a transglycosidic hydrogen bond O2 '...HO3 was proven by the presence of a cross-peak in H-1,C-13 HSQC-TOCSY experiments as a result of direct TOCSY transfer between HO3 of the reducing end residue and H2 ' (detected at C2 ') of the terminal residue. The occurrence of inter-residue hydrogen bonding, albeit transient, is judged important for the stabilization of three-dimensional structures, which may be essential in maintaining a conformational state for carbohydrate-protein interactions of glycans to take place in biologically important environments.

  • 15.
    Rönnols, Jerk
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pendrill, Robert
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Fontana, Carolina
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Hamark, Christoffer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Angles d'Ortoli, Thibault
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ståhle, Jonas
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Zaccheus, Mona V.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Säwén, Elin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Hahn, Liljan E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Iqbal, Shahzad
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Complete H-1 and C-13 NMR chemical shift assignments of mono- to tetrasaccharides as basis for NMR chemical shift predictions of oligosaccharides using the computer program CASPER2013In: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 380, p. 156-166Article in journal (Refereed)
    Abstract [en]

    H-1 and C-13 NMR chemical shift data are used by the computer program CASPER to predict chemical shifts of oligo- and polysaccharides. Three types of data are used, namely, those from monosaccharides, disaccharides, and trisaccharides. To improve the accuracy of these predictions we have assigned the H-1 and C-13 NMR chemical shifts of eleven monosaccharides, eleven disaccharides, twenty trisaccharides, and one tetrasaccharide; in total 43 compounds. Five of the oligosaccharides gave two distinct sets of NMR resonances due to the alpha- and beta-anomeric forms resulting in 48 H-1 and C-13 NMR chemical shift data sets. In addition, the pyranose ring forms of Neu5Ac were assigned at two temperatures, due to chemical shift displacements as a function of temperature. The H-1 NMR chemical shifts were refined using total line-shape analysis with the PERCH NMR software. H-1 and C-13 NMR chemical shift predictions were subsequently carried out by the CASPER program (http://www.casper.organ.su.se/casper/) for three branched oligosaccharides having different functional groups at their reducing ends, namely, a mannose-containing pentasaccharide, and two fucose-containing heptasaccharides having N-acetyllactosamine residues in the backbone of their structures. Good to excellent agreement was observed between predicted and experimental H-1 and C-13 NMR chemical shifts showing the utility of the method for structural determination or confirmation of synthesized oligosaccharides.

  • 16. Tavagnacco, Letizia
    et al.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Schnupf, Udo
    Saboungi, Marie-Louise
    Himmel, Michael
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cesaro, Attilio
    Brady, John W.
    Caffeine and Sugars Interact in Aqueous Solutions: A Simulation and NMR Study2012In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 38, p. 11701-11711Article in journal (Refereed)
    Abstract [en]

    Molecular dynamics simulations were carried out on several systems of caffeine interacting with simple sugars. These included a single caffeine molecule in a 3 in solution of alpha-D-glucopyranose, at a caffeine concentration of 0.083 m, a single caffeine in a 3 in solution of beta-D-glucopyranose, and a single caffeine molecule in a 1.08 m solution of sucrose (table sugar). Parallel nuclear magnetic resonance titration experiments were carried out on the same solutions under similar conditions. Consistent with previous thermodynamic experiments, the sugars were found to have an affinity for the caffeine molecules in both the simulations and experiments, and the binding in these complexes occurs by face-to-face stacking of the hydrophobic triad of protons of the pyranose rings against the caffeine face, rather than by hydrogen bonding. For the disaccharide, the binding occurs via stacking of the glucose ring against the caffeine, with a lesser affinity for the fructose observed. These findings are consistent with the association being driven by hydrophobic hydration and are similar to the previously observed binding of glucose rings to various other planar molecules, including indole, serotonin, and phenol.

  • 17. Wu, Emilia L.
    et al.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Jo, Sunhwan
    Stuhlsatz, Danielle
    Yeom, Min Sun
    Klauda, Jeffery B.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Im, Wonpil
    Molecular Dynamics and NMR Spectroscopy Studies of E. coli Lipopolysaccharide Structure and Dynamics2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 105, no 6, p. 1444-1455Article in journal (Refereed)
    Abstract [en]

    Lipopolysaccharide (LPS), a component of Gram-negative bacterial outer membranes, comprises three regions: lipid A, core oligosaccharide, and O-antigen polysaccharide. Using the CHARMM36 lipid and carbohydrate force fields, we have constructed a model of an Escherichia coil R1 (core) 06 (antigen) LPS molecule. Several all-atom bilayers are built and simulated with lipid A only (LIPA) and varying lengths of 0 (LPS0), 5 (LPS5), and 10 (LPS10) O6 antigen repeating units; a single unit of 06 antigen contains five sugar residues. From H-1,H-1-NOESY experiments, cross-relaxation rates are obtained from an O-antigen polysaccharide sample. Although some experimental deviations are due to spin-diffusion, the remaining effective proton-proton distances show generally very good agreement between NMR experiments and molecular dynamics simulations. The simulation results show that increasing the LPS molecular length has an impact on LPS structure and dynamics and also on LPS bilayer properties. Terminal residues in a LPS bilayer are more flexible and extended along the membrane normal. As the core and O-antigen are added, per-lipid area increases and lipid bilayer order decreases. In addition, results from mixed LPS0/5 and LPS0/10 bilayer simulation's show that the LPS O-antigen conformations at a higher concentration of LPS5 and LPS10 are more orthogonal to the membrane and less flexible. The O-antigen concentration of mixed LPS bilayers does not have a significant effect on per-lipid area and hydrophobic thickness. Analysis of ion and water penetration shows that water molecules can penetrate inside the inner core region, and hydration is critical to maintain the integrity of the bilayer structure.

1 - 17 of 17
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf