| 1. |
- Arja, Katriann, et al.
(författare)
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Synthesis and Characterization of Oligothiophene-Porphyrin-Based Molecules That Can Be Utilized for Optical Assignment of Aggregated Amyloid-beta Morphotypes
- 2018
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Ingår i: Frontiers in Chemistry. - : FRONTIERS MEDIA SA. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Molecular tools for fluorescent imaging of protein aggregates are essential for understanding the significance of these pathological hallmarks in proteopathic neurodegenerative diseases, such as Alzheimers disease. Here, we report the synthesis of a series of oligothiophene porphyrin hybrids, OTPHs, and the evaluation of these dyes for fluorescent imaging of beta-amyloid aggregates in tissue sections from a transgenic mouse model with Alzheimers disease pathology. The OTPHs proved to be successful for spectral and lifetime imaging assessment of protein deposits and our findings confirm that the enhanced spectral range and distinct lifetime diversity of these novel tools allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye. In addition, the chemical identity of the porphyrin moiety, as well as the spacing between the two optical active moieties, influenced the OTPHs performance for fluorescent assignment of the protein deposits. We foresee that our findings will aid in the chemical design of dyes that can be utilized as optical tools for studying the polymorphic nature of protein aggregates associated with proteopathic neurodegenerative diseases.
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| 2. |
- Cao, Lili, et al.
(författare)
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On the difference between additive and subtractive QM/MM calculations
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6:APR
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Tidskriftsartikel (refereegranskat)abstract
- The combined quantum mechanical (QM) and molecular mechanical (MM) approach (QM/MM) is a popular method to study reactions in biochemical macromolecules. Even if the general procedure of using QM for a small, but interesting part of the system and MM for the rest is common to all approaches, the details of the implementations vary extensively, especially the treatment of the interface between the two systems. For example, QM/MM can use either additive or subtractive schemes, of which the former is often said to be preferable, although the two schemes are often mixed up with mechanical and electrostatic embedding. In this article, we clarify the similarities and differences of the two approaches. We show that inherently, the two approaches should be identical and in practice require the same sets of parameters. However, the subtractive scheme provides an opportunity to correct errors introduced by the truncation of the QM system, i.e., the link atoms, but such corrections require additional MM parameters for the QM system. We describe and test three types of link-atom correction, viz. for van der Waals, electrostatic, and bonded interactions. The calculations show that electrostatic and bonded link-atom corrections often give rise to problems in the geometries and energies. The van der Waals link-atom corrections are quite small and give results similar to a pure additive QM/MM scheme. Therefore, both approaches can be recommended.
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| 3. |
- Karasu, Feyza, et al.
(författare)
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Organic-inorganic hybrid planarization and water vapor barrier coatings on cellulose nanofibrils substrates
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Cellulose nanofibrils (CNF) can be produced in the form of thin, transparent andflexible films. However, the permeability of such materials to oxygen and water vaporis very sensitive to moisture, which limits their potential for a variety of packaging andencapsulation applications. Diffusion barrier coatings were thus developed to reducethe access of water molecules to enzymatically pre-treated and carboxymethylated CNFsubstrates. The coatings were based on UV curable organic-inorganic hybrids withepoxy, tetraethylorthosilicate (TEOS) and 3-glycidoxypropyltrimethylenesilane (GPTS)precursors and additional vapor formed SiNx layers. A total of 14 monolayer andmultilayer coatings with various thickness and hybrid composition were produced andanalyzed. The water vapor transmission rate (WVTR) of the bilayer epoxy/CNF film wastwo times lower compared to that of uncoated CNF film. This was partly due to the watervapor permeability of the epoxy, a factor of two times lower than CNF. The epoxy coatingimproved the transparency of CNF, however it did not properly wet to the CNF surfacesand the interfacial adhesion was low. In contrast hybrid epoxy-silica coatings led to highadhesion levels owing to the formation of covalent interactions through condensationreactions with the OH-terminated CNF surface. The barrier and optical performance ofhybrid coated CNF substrates was similar to that of CNF coated with pure epoxy. Inaddition, the hybrid coatings provided an excellent planarization effect, with roughnessclose to 1 nm, one to two orders of magnitude lower than that of the CNF substrates.The WVTR and oxygen transmission rate values of the hybrid coated CNF laminateswere in the range 5–10 g/m2/day (at 38◦C and 50% RH) and 3–6 cm3/m2/day/bar (at23◦C and 70% RH), respectively, which matches food and pharmaceutical packagingrequirements. The permeability to water vapor of the hybrid coatings wasmoreover foundto decrease with increasing the TEOS/GPTS ratio up to 30 wt% and then increase athigher ratio, and to be much lower for thinner coatings due to further UV-induced silanolcondensation and faster evaporation of byproducts. The addition of a single 150 nmthickSiNx layer on the hybrid coated CNF improved its water vapor barrier performance bymore than 680 times, with WVTR below the 0.02 g/m2/day detection limit.
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| 4. |
- Karnaouri, Anthi C, et al.
(författare)
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Fine-tuned enzymatic hydrolysis of organosolv pretreated forest materials for the efficient production of cellobiose
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Non-digestible oligosaccharides (NDOs) are likely prebiotic candidates that have been related to the prevention of intestinal infections and other disorders for both humans and animals. Lignocellulosic biomass is the largest carbon source in the biosphere, therefore cello-oligosacharides (COS), especially cellobiose, are potentially the most widely available choice of NDOs. Production of COS and cellobiose with enzymes offers numerous benefits over acid-catalyzed processes, as it is milder, environmentally friendly and produces fewer by-products. Cellobiohydrolases (CBHs) and a class of endoglucanases (EGs), namely processive EGs, are key enzymes for the production of COS, as they have higher preference toward glycosidic bonds near the end of cellulose chains and are able to release soluble products. In this work, we describe the heterologous expression and characterization of two CBHs from the filamentous fungus Thermothelomyces thermophila, as well as their synergism with proccessive EGs for cellobiose release from organosolv pretreated spruce and birch. The properties, inhibition kinetics and substrate specific activities for each enzyme are described in detail. The results show that a combination of EGs belonging to Glycosyl hydrolase families 5, 6 and 9, with a CBHI and CBHII in appropriate proportions, can enhance the production of COS from forest materials, underpinning the potential of these biocatalysts in the production of NDOs.
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| 5. |
- Malekian, Bita, 1986, et al.
(författare)
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Detecting Selective Protein Binding Inside Plasmonic Nanopores: Toward a Mimic of the Nuclear Pore Complex
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6:December 2018
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Tidskriftsartikel (refereegranskat)abstract
- Biosensors based on plasmonic nanostructures offer label-free and real-time monitoring of biomolecular interactions. However, so do many other surface sensitive techniques with equal or better resolution in terms of surface coverage. Yet, plasmonic nanostructures offer unique possibilities to study effects associated with nanoscale geometry. In this work we use plasmonic nanopores with double gold films and detect binding of proteins inside them. By thiol and trietoxysilane chemistry, receptors are selectively positioned on the silicon nitride interior walls. Larger (similar to 150 nm) nanopores are used detect binding of averaged sized proteins (similar to 60 kg/mol) with high signal to noise (>100). Further, we fabricate pores that approach the size of the nuclear pore complex (diameter down to 50 nm) and graft disordered phenylalanine-glycine nucleoporin domains to the walls, followed by titration of karyopherin beta 1 transport receptors. The interactions are shown to occur with similar affinity as determined by conventional surface plasmon resonance on planar surfaces. Our work illustrates another unique application of plasmonic nanostructures, namely the possibility to mimic the geometry of a biological nanomachine with integrated optical sensing capabilities.
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| 6. |
- McNamee, Cathy E., et al.
(författare)
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Rice starch particle interactions at air/aqueous interfaces-effect of particle hydrophobicity and solution ionic strength
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6:MAY
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Tidskriftsartikel (refereegranskat)abstract
- Starch particles modified by esterification with dicarboxylic acids to give octenyl succinic anhydride (OSA) starch is an approved food additive that can be used to stabilize oil in water emulsions used in foods and drinks. However, the effects of the OSA modification of the starch particle on the interfacial interactions are not fully understood. Here, we directly measured the packing of films of rice starch granules, i.e., the natural particle found inside the plant, at air/aqueous interfaces, and the interaction forces in that system as a function of the particle hydrophobicity and ionic strength, in order to gain insight on how starch particles can stabilize emulsions. This was achieved by using a combined Langmuir trough and optical microscope system, and the Monolayer Interaction Particle Apparatus. Native rice starch particles were seen to form large aggregates at air/water interfaces, causing films with large voids to be formed at the interface. The OSA modification of the rice starches particles decreased this aggregation. Increasing the degree of modification improved the particle packing within the film of particles at the air/water interface, due to the introduction of inter-particle electrostatic interactions within the film. The introduction of salt to the water phase caused the particles to aggregate and form holes within the film, due to the screening of the charged groups on the starch particles by the salt. The presence of these holes in the film decreased the stiffness of the films. The effect of the OSA modification was concluded to decrease the aggregation of the particles at an air/water interface. The presence of salts, however, caused the particles to aggregate, thereby reducing the strength of the interfacial film.
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| 7. |
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| 8. |
- Planas, Ferran, et al.
(författare)
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A Theoretical Study of the Benzoylformate Decarboxylase Reaction Mechanism
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Density functional theory calculations are used to investigate the detailed reaction mechanism of benzoylformate decarboxylase, a thiamin diphosphate (ThDP)-dependent enzyme that catalyzes the nonoxidative decarboxylation of benzoylformate yielding benzaldehyde and carbon dioxide. A large model of the active site is constructed on the basis of the X-ray structure, and it is used to characterize the involved intermediates and transition states and evaluate their energies. There is generally good agreement between the calculations and available experimental data. The roles of the various active site residues are discussed and the results are compared to mutagenesis experiments. Importantly, the calculations identify off-cycle intermediate species of the ThDP cofactor that can have implications on the kinetics of the reaction.
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| 9. |
- Sheng, Xiang, et al.
(författare)
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Reaction Mechanism and Substrate Specificity of Iso-orotate Decarboxylase : A Combined Theoretical and Experimental Study
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The C-C bond cleavage catalyzed by metal-dependent iso-orotate decarboxylase (IDCase) from the thymidine salvage pathway is of interest for the elucidation of a (hypothetical) DNA demethylation pathway. IDCase appears also as a promising candidate for the synthetic regioselective carboxylation of N-heteroaromatics. Herein, we report a joint experimental-theoretical study to gain insights into the metal identity, reaction mechanism, and substrate specificity of IDCase. In contrast to previous assumptions, the enzyme is demonstrated by ICPMS/MS measurements to contain a catalytically relevant Mn(2+)rather than Zn2+. Quantum chemical calculations revealed that decarboxylation of the natural substrate (5-carboxyuracil) proceeds via a (reverse) electrophilic aromatic substitution with formation of CO2. The occurrence of previously proposed tetrahedral carboxylate intermediates with concomitant formation of HCO3- could be ruled out on the basis of prohibitively high energy barriers. In contrast to related o-benzoic acid decarboxylases, such as y-resorcylate decarboxylase and 5-carboxyvanillate decarboxylase, which exhibit a relaxed substrate tolerance for phenolic acids, IDCase shows high substrate fidelity. Structural and energy comparisons suggest that this is caused by a unique hydrogen bonding of the heterocyclic natural substrate (5-carboxyuracil) to the surrounding residues. Analysis of calculated energies also shows that the reverse carboxylation of uracil is impeded by a strongly disfavored uphill reaction.
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| 10. |
- Siegbahn, Per E. M., et al.
(författare)
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A Systematic DFT Approach for Studying Mechanisms of Redox Active Enzymes
- 2018
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Ingår i: Frontiers in Chemistry. - : Frontiers Media SA. - 2296-2646. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- When DFT has been applied to study mechanisms of redox processes a common procedure has been to study the results for many different functionals. For redox reactions involving the first row transition metals, this approach has given very different results for different functionals. The conclusion has been that DFT cannot be used for these reactions. In the meantime, results with strong predictability have been generated, most noteworthy for photosystem II, where all DFT predictions have been verified by experiments performed later. In order to obtain these predictive results using DFT, an alternative, systematic approach has been used, where the key differences between the results for different functionals can be rationalized by using a single parameter, rather than using the very large number of differences in the functionals.
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