| 1. |
- Andersson, Hanna, 1979, et al.
(författare)
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Assessing the Ability of Spectroscopic Methods to Determine the Difference in the Folding Propensities of Highly Similar beta-Hairpins
- 2017
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Ingår i: Acs Omega. - : American Chemical Society (ACS). - 2470-1343. ; 2:2, s. 508-516
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Tidskriftsartikel (refereegranskat)abstract
- We have evaluated the ability of nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopies to describe the difference in the folding propensities of two structurally highly similar cyclic beta-hairpins, comparing the outcome to that of molecular dynamics simulations. NAMFIS-type NMR ensemble analysis and CD spectroscopy were observed to accurately describe the consequence of altering a single interaction site, whereas a single-site C-13 NMR chemical shift melting curve-based technique was not.
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| 2. |
- Andersson, Hanna, Dr. 1979-, et al.
(författare)
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Binding of 2-(Triazolylthio)acetamides to Metallo-beta-lactamase CcrA Determined with NMR
- 2020
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:34, s. 21570-21578
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Tidskriftsartikel (refereegranskat)abstract
- Metallo-beta-lactamase (MBL)-producing bacteria resistant to beta-lactam antibiotics are a serious threat to human health. Despite great efforts and important progress in the discovery of MBL inhibitors (MBLIs), there is none in clinical use. Herein, inhibitor complexes of the MBL CcrA were investigated by NMR spectroscopy to provide perspectives on the further development of 2-(triazolylthio)acetamide-type MBLIs. By using the NMR-based chemical shift perturbation (CSP) and direction of CSP methodologies together with molecular docking, the spatial orientation of three compounds in the CcrA active site was investigated (4-6). Inhibitor 6 showed the best binding affinity (K-d approximate to 2.3 +/- 0.3 mu M), followed by 4 (K-d approximate to 11 +/- 11 mu M) and 5 (K-d = 34 +/- 43 mu M), as determined from the experimental NMR data. Based on the acquired knowledge, analogues of other MBLIs (1-3) were designed and evaluated in silico with the purpose of examining a strategy for promoting their interactions with the catalytic zinc ions.
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| 3. |
- Andersson, Martin, 1974, et al.
(författare)
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Vesicle and bilayer formation of diphytanoylphosphatidylcholine (DPhPC) and diphytanoylphosphatidylethanolamine (DPhPE) mixtures and their bilayers' electrical stability
- 2011
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Ingår i: Colloids and Surfaces B: Biointerfaces. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 82:2, s. 550-561
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Tidskriftsartikel (refereegranskat)abstract
- Lipid bilayers are of interest in applications where a cell membrane mimicking environment is desired. The performance of the lipid bilayer is largely dependent on the physical and chemical properties of the component lipids. Lipid bilayers consisting of phytanoyl lipids have proven to be appropriate choices since they exhibit high mechanical and chemical stability. In addition, such bilayers have high electrical resistances. Two different phytanoyl lipids, 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) and 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine(DPhPE), and various combinations of the two have been investigated with respect to their behavior in aqueous solutions, their interactions with solid surfaces, and their electrical stability. Dynamic light scattering, nuclear magnetic resonance diffusion, and cryogenic transmission electron microscopy measurements showed that pure DPhPC as well as mixtures of DPhPC and DPhPE consisting of greater than 50% (mol%) DPhPC formed unilamellar vesicles. If the total lipid concentration was greater than 0.15 g/l, then the vesicles formed solid-supported bilayers on plasma-treated gold and silica surfaces by the process of spontaneous vesicle adsorption and rupture, as determined by quartz crystal microbalance with dissipation monitoring and atomic force microscopy. The solid-supported bilayers exhibited a high degree of viscoelasticity, probably an effect of relatively high amounts of imbibed water or incomplete vesicle fusion. Lipid compositions consisting of greater than 50% DPhPE formed small flower-like vesicular structures along with discrete liquid crystalline structures, as evidenced by cryogenic transmission electron microscopy. Furthermore, electrophysiology measurements were performed on bilayers using the tip-dip methodology and the bilayers' capacity to retain its electrical resistance towards an applied potential across the bilayer was evaluated as a function of lipid composition. It was shown that the lipid ratio significantly affected the bilayer's electrical stability, with pure DPhPE having the highest stability followed by 3DPhPC:7DPhPE and 7DPhPC:3DPhPE in decreasing order. The bilayer consisting of 5DPhPC:5DPhPE had the lowest stability towards the applied electrical potential.
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| 4. |
- Bender, Johanna, 1975, et al.
(författare)
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Structure and dynamics of a sponge phase in the methyl delta-aminolevulinate/monoolein/water/propylene glycol system
- 2008
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 17:2, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- The structural effect caused by the addition of up to 16% (w/w) of the hydrochloride salt of delta-aminolevulinic acid (ALA, HOOC-CH(2)-CH(2)-CO-CH(2)-NH(2)HCl) or its methyl ester (m-ALA) to the sponge phase formed of monoolein/water/propylene glycol was investigated by means of crossed polarizers, small angle X-ray diffraction (SAXD) and nuclear magnetic resonance diffusometry (NMRD). Inspection with crossed polarizers revealed that additions of 4-16% (w/w) m-ALA transformed the isotropic bicontinuous sponge phase partly (4-10%) or completely (13 and 16%) into an anisotropic lamellar phase, indicating that m-ALA has a flattening effect on the bilayer curvature. The addition of 16% (w/w) ALA did not show any effect on the sponge phase. By addition of water to the anisotropic m-ALA samples, isotropic liquids were re-formed. The SAXD data for the isotropic liquids showed a diffuse Bragg peak and the NMRD self-diffusion coefficients for the drug (m-ALA) and the components of the original sponge phase (monoolein, water and propylene glycol) were shown to be essentially constant for 0-16% (w/w) added m-ALA. These results confirmed the hypothesis that the re-formed isotropic phases were indeed sponge phases. Water, for example, showed a diffusion coefficient of 3.1-3.9x10(-10)m(2)s(-1) in the sponge phase, compared to 5.3-5.7x10(-10)m(2)s(-1) in relevant water/propylene glycol solutions or 2.3x10(-9)m(2)s(-1) in pure water. The reduction can be explained as a consequence of the microstructure (congruent monoolein bilayer) of the sponge phase and of the viscosity effect caused by propylene glycol and m-ALA.
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| 5. |
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| 6. |
- Danelius, Emma, et al.
(författare)
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Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation
- 2017
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 56:25, s. 3265-3272
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Tidskriftsartikel (refereegranskat)abstract
- Halogen bonding is a weak chemical force that has so far mostly found applications in crystal engineering. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a beta-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.
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| 7. |
- Jarvoll Dae, Patrik, 1971
(författare)
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Mass Transport Properties in Supramolecular Systems Studied by Diffusion and Relaxation NMR
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis shows how diffusion and relaxation NMR can be applied in various aspects to study mass transport in supramolecular systems. Information about these systems can be obtained, either by direct measurement of the molecules that are incorporated in a supramolecular structure, or via probe molecules, which indirectly gives information about the system. Through the relation between molecular size and diffusion, probes can be used for the evaluation of sizes of objects in solution. This was demonstrated in Paper III, where vesicles were characterized with respect to size using diffusion measurements. By measuring diffusion as a series of various observation times, the exchange dynamics of a molecule between two separate environments with different diffusion can be investigated and mean residence times can be extracted. In Paper I it is shown that organosilica nanoparticles, synthesized with and without oil, can take up triethylamine and tributylamine from water solutions. The mean residence times were longer in particles compared to in the bulk, and significantly longer for particles synthesized in the presence of oil. The diffusion and relaxation of molecules in self-assembled structures, such as microemulsions and L3-phases, can reveal information about the microstructure in the system. Paper IV, shows that up to 16% of a drug compound (δ-aminolevulinic acid) could be added to a propylene glycol/monoolein/water system, without affecting the L3-phase. In Paper II, the lipid composition was varied in a water-in-oil microemulsion. At high concentration of triglycerides of medium chain length a microstructure that slowed down the water diffusion was formed. This was also observed with T2 relaxation as well as by chemical shift changes as seen by routine 1D-1H NMR experiments.In Paper VI transport of hexamethyldisilane in mucus and mucin showed that surfactants are of high importance in the transport mechanism in mucus. Measuring the diffusion of a probe in a complex network structure may reveal information about the actual environment in which it is diffusing. In Paper V, dendrimers were shown to be suitable for probing polymer hydrogels. The susceptibility effect was also investigated in a magnetic field study in which the 1H Larmor frequency was varied from 400 to 900 MHz.
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| 8. |
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| 9. |
- Loren, Niklas, et al.
(författare)
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Dendrimer diffusion in ?-carrageenan gel structures
- 2009
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 10:2, s. 275-284
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the ?-carrageenan concentration on gel microstructure and self-diffusion of polyamideamine dendrimers has been determined by transmission electron microscopy (TEM), image analysis, and nuclear magnetic resonance (NMR) diffusometry. Different salt conditions of KCl, NaCl, and mixtures thereof allowed for formation of significantly different microstructures. The ?-carrageenan concentrations were varied between 0.25 and 3.0 w/w% for a salt mixture containing 20 mM KCl and 200 mM NaCl gels and between 0.5 and 4.0 w/w% for 250 mM NaCl gels. Furthermore, the effect of potassium ion concentration on the gel structure and the dendrimer diffusion rate was determined. The potassium ion concentration was varied between 20 mM KCl and 200 mM KCl. Two different dendrimer generations with significant difference in size were used: G2 and G6. Dendrimers were found to be sensitive probes for determination of the effect of the gel microstructure on molecular diffusion rate. A qualitative comparison between TEM micrographs, NMR diffusometry data and image analysis showed that the gel structure has a large impact on the dendrimers diffusion in ?-carrageenan gels. It was found that diffusion was strongly influenced by the ?-carrageenan concentration and the dendrimer generation. Small voids in the gel network gave strongly reduced diffusion. Image analysis revealed that the interfacial area between the gel network and the surrounding water phase correlated well with the dendrimer diffusion. © 2009 American Chemical Society.
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| 10. |
- Lundberg, Dan, 1975, et al.
(författare)
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Structural Evolution of Oleyl Betainate Aggregates: In Situ Formation of Small Unilamellar Vesicles
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 26:11, s. 7996-8001
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Tidskriftsartikel (refereegranskat)abstract
- Betaine esters prepared from long-chain alcohols are a class of hydrolyzable cationic surfactants that is interesting both because the compounds can be designed to give harmless products on degradation and that the hydrolysis products can induce potentially useful changes in the properties of systems where such surfactants are present. In this work, the evolution in structure of aggregates formed by oleyl betainate during hydrolysis of the compound has been investigated using H-1 NMR and cryo-transmission electron microscopy (cryo-TEM). With an increasing extent of hydrolysis, and thus an increasing fraction of oleyl alcohol in the aggregates, the aggregate structure changes in a sequence consistent with an increase in the average packing parameter of the surfactant-alcohol mixture, from spherical micelles, via wormlike micelles, to vesicles. An important result front this work is that it demonstrates a means of in situ production of small unilamellar vesicles with a rather narrow size distribution.
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