Influence Of Small Molecules Research Articles

Inhibition of the Peroxygenase Lytic Polysaccharide Monooxygenase by Carboxylic Acids and Amino Acids.

Lytic polysaccharide monooxygenases (LPMOs) are widely distributed in fungi, and catalyze the oxidative degradation of polysaccharides such as cellulose. Despite their name, LPMOs possess a dominant peroxygenase activity that is reflected in high turnover numbers but also causes deactivation. We report on the influence of small molecules and ions on the activity and stability of LPMO during catalysis. Turbidimetric and photometric assays were used to identify LPMO inhibitors and measure their inhibitory effect. Selected inhibitors were employed to study LPMO activity and stability during cellulose depolymerization by HPLC and turbidimetry. It was found that the fungal metabolic products oxalic acid and citric acid strongly reduce LPMO activity, but also protect the enzyme from deactivation. QM calculations showed that the copper atom in the catalytic site could be ligated by bi- or tridentate chelating compounds, which replace two water molecules. MD simulations and QM calculations show that the most likely inhibition pattern is the competition between the inhibitor and reducing agent in the oxidized Cu(II) state. A correlation between the complexation energy and the IC50 values demonstrates that small, bidentate molecules interact strongest with the catalytic site copper and could be used by the fungus as physiological effectors to regulate LPMO activity.

Influence of small molecules on the photo-stability of water soluble porcine lens proteins.

The eye lens is a biconvex structure composed of lens fibres, cells that lack of blood and nerve supply and of any organelle, allowing for a high concentration of water soluble proteins that determine the lens transparency and refractive index. The lens water soluble protein pool in mammals is composed of α-, β-, and γ-crystallins, the latter being involved in calcium homeostasis and having structural importance, the first playing a crucial role in preventing protein aggregation and the consequent lens obfuscation, which leads to the clinical outcome of cataract. Among different factors, oxidative stress, free radicals, and reactive oxygen species (ROSs) generated by the exposure to UV light are widely recognized to cause cataract formation. Taking advantage of synchrotron radiation circular dichroism, fluorescence, and circular dichroism spectroscopies, in the present study we investigate the influence of different small molecules with the potential to either quench ROS generation or to stabilize protein conformation. Therefore, ascorbic acid, an excellent antioxidant agent already present in the eye aqueous humour, has been tested along with ceftriaxone, mannitol and trehalose, which osmolyte activity was demonstrated interfering with model proteins misfolding. Our results showed that ascorbic acid strongly inhibits the ROS production without, however, preserving the native protein structure, whereas mannitol had no effect on the ROS production but retained better the secondary structure of WS proteins. Collectively, the use of a mixture of ascorbic acid and mannitol could be used to better protect eye lens proteins from ROS damage preventing the cataract onset.

Facile Route for the Fabrication of Polypropylene Separators for Lithium-Ion Batteries with High Elongation and Strong Puncture Resistance

A facile route for fabrication of polypropylene separators for lithium-ion batteries with high elongation and strong puncture resistance has been proposed in this work. Polypropylene separators immersed in paraffin wax have been prepared to introduce small molecules into separators. The influence of small molecules on mechanical properties of separators is studied in this work. The elongation at break stretched in the transverse direction of separators significantly increases for more than 300% while the puncture depth and force increases 50% after treatment with paraffin wax for 2 h. Meanwhile, no clear change of the pore structure can be seen after the treatment. The mechanism behind it has been discussed as well. Moreover, comprehensive performance of batteries equipped with modified separators has been evaluated. The modified separators exhibit same electrochemical performances compared to original separators. Generally, paraffin modification is a facile and effective route for mechanical enhancement of separators without sacrificing comprehensive electrochemical properties.

Precipitation of complex antibody solutions: influence of contaminant composition and cell culture medium on the precipitation behavior

Preparative protein precipitation is known as a cost-efficient and easy-to-use alternative to chromatographic purification steps. This said, at the moment, there is no process for monoclonal antibodies (mAb) on the market, although especially polyethylene glycol-induced precipitation has shown great potential. One reason might be the highly complex behavior of each component of a crude feedstock during the precipitation process. For different investigated mAbs, significant variations in the host cell protein (HCP) reduction are observed. In contrast to the precipitation behavior of single components, the interactions and interplay in a complex feedstock are not fully understood yet. This work discusses the influence of contaminants on the precipitation behavior of two different mAbs, an IgG1, and an IgG2. By spiking the mAbs with mock solution, a complex feedstock could successfully be mimicked. Spiking contaminants influenced the yield and purity of the mAbs after the precipitation step, compared to the precipitation behavior of the single components. The mixture showed a decrease in the contaminant and mAb solubility. By re-buffering the mock solution prior to spiking, special salts, small molecules like amino acids, vitamins, or sugars could be depleted while larger ones like HCP or DNA were still present. Therefore, it was possible to distinguish the influence of small molecules and larger ones. Hence, mAb–macromolecular interaction could be identified as a possible reason for the observed higher precipitation propensity, while small molecules of the cell culture medium were identified as solubilisation factors during the precipitation process.

Effect of concentration of DH6T on the performance of photoconductor fabricated using blends of P3HT and DH6T

The influence of small molecule (SM) α, ω-di-hexyl-sexithiophene (DH6T) concentration, in the blends of conjugated polymer (CP) poly (3-hexylthiophene) (P3HT) and DH6T, was investigated in terms of barrier potential reduction and improved photoresponse of the fabricated photoconductor using these blends. Barrier potential in Au/P3HT:DH6T/Au device structure, occurring at the interface of Au (top)/P3HT:DH6Twas estimated by Fowler Nordheim (FN) tunneling model-based analysis of I-V characteristics. The barrier potential of the fabricated device was observed to decrease upon addition of a small quantity of DH6T in comparison to the pristine polymer-based device. This reduction in barrier was attributed to the improved ordering and morphology of the polymer chains upon blending it with an SM. The variation in the ordering of the polymer chains was further confirmed with Photoluminescence spectroscopy, Absorption spectroscopy, and XRD data. Subsequently, it was also observed that only up to a definite SM concentration (25% in this study) ordering of polymer chains improved causing a reduction in barrier potential and subsequent improvement in the photoresponse of the fabricated devices. Finally, it was observed that the optimized blending of CP and SM could to be useful in reducing the effect of penetration of Au inside the CP matrix in the top contact configuration thereby resulting in the reduction of a barrier for carrier injection which is generally lower in the bottom contact configurations. These studies are critical from the point of view of the development of photoconductors and photosensitive top contact organic field effect transistors (OFETs).

Target Engagement of Small Molecules: Thermal Profiling Approaches on Different Levels.

The identification of protein targets and the elucidation of the molecular mechanism of action (MMoA) of bioactive small molecules are central goals of chemical biology. Many different techniques for target identification and engagement are developed, but none of them is generic. Here we describe one of these techniques-the cellular thermal shift assay (CETSA). The assay works without any labeling of proteins or small molecules, which allows the investigation of the unaltered interaction between the interaction partners. Briefly, the influence of small molecules on the thermal stability of proteins within whole cell lysates is investigated. We describe this approach in two variants: the conventional immunoblot-based approach (CETSA), as well as an unbiased approach based on a proteome-wide mass spectrometric analysis (thermal proteome profiling, TPP). The CETSA approach requires preknowledge about possible target proteins and can only detect a few proteins at once. Although TPP is technically more demanding, it allows for the identification of multiple (off)targets without any preknowledge.

Protein interaction in the mechanism of platinum anticancer drugs

Platinum anti-tumor drugs are widely used in cancer chemotherapy. These compounds are believed to induce apoptosis in tumor cells by DNA crosslinking, which causes DNA damage and suppresses DNA replication. However, recent studies indicate that platinum drugs can react with a large variety of intracellular and extracellular proteins before binding to the nuclear DNA. These protein interactions can alter the transportation and metabolism of platinum drugs as well as their interactions with the DNA target, which have significant influence on the efficacy and resistance of platinum drugs. On the other hand, platinum reactions can alter the function of proteins, which contributes to the drug efficacy and side-effects of platinum drugs. In this article, we review the recent progress in the protein interaction of platinum drugs. The influence of small molecules on the reaction, the reaction of non-cancer target proteins, and the research methods for the investigation are also discussed.

Determining the Influence of Small Molecules on Hypoxic Prostate Cancer Cell (DU-145) Viability Using Automated Cell Counting and a Cell Harvesting Protocol

Determining the Influence of Small Molecules on Hypoxic Prostate Cancer Cell (DU-145) Viability Using Automated Cell Counting and a Cell Harvesting Protocol

Influence of Small Molecules in Conducting Polyaniline on the Photovoltaic Properties of Solid-State Dye-Sensitized Solar Cells

Solid-state dye-sensitized solar cells (DSSCs) were fabricated using 4-dodecylbenzenesulfonic acid-doped polyaniline (PANI−DBSA) blended with LiI and 4-tert-butylpyridine (tBP) as hole conductors. The introduction of LiI and tBP into the polymer improves the photovoltaic behavior of solid-state DSSCs significantly. Compared with a DSSC only using PANI−DBSA as a hole conductor, one with LiI added at the optimum concentration gives an overall solar-to-electric energy conversion efficiency (ηe) increased by a factor of 5.13, whereas one with both LiI and tBP added at the optimum concentrations gives an ηe increased by a factor of 6.6 and a maximum value of the incident photon to current conversion efficiency increased 100%. In addition, the photovoltage and photocurrent transients are determined to investigate the influence of LiI and tBP in PANI−DBSA on the photovoltaic performance of solid-state DSSCs.

Fumed silica synthesis: influence of small molecules on the particle formation process

Burning silicon tetrachloride in an oxygen-hydrogen flame produces fumed silica. This process is known for at least 50 years [1-5], but some important details are still uncertain. We would like to study several starting steps of fumed silica synthesis on the way from molecules to products. To do this we have performed quantum-level simulations of protoparticle and primary particle formation, from silicon dioxide molecules. Additionally, we have simulated the behavior of silica clusters in the presence of small molecules like water and hydrochloric acid. The reaction of silicon dioxide molecules leads to a silica cluster, which is covered with chemicaly highly active sites of one-coordinated oxygen atoms and three-coordinated silicon atoms. These clusters interact together and produce silica bulk like quartz glass. Reaction with water terminates the silica particle surface and leads to a complicated structure of the particle surfaces. The hydroxyl shell protects the particle body against the increase in particle size, but leads to aggregate and agglomerate formation.

Polymer-polymer interactions and the influence of small molecules on the complexation reaction

The process of complexation, whereby two polymer molecules interact physically to form a complex often with physical properties quite different from those of its constituents, has been studied with reference to poly(acrylic acid) and polyvinylpyrrolidone systems. Both the degree of linkage, θ, defined as the ratio of the bound groups to the total of potentially interacting groups, and the stability constant K of such complexes in solution in water and DMF have been determined as a function of temperature by means of potentiometric titration. It was found that θ and K are strongly dependent on temperature and the nature of the medium and that the hydrophobic interaction is a significant factor in the stabilization of the polycomplexes. The influence of small molecules on the complexation reaction has also been investigated and depending on the solvent employed, is shown to be great. Enthalpy and entropy changes of the systems were also calculated.

A scanning calorimetric study of small molecule-lipid bilayer mixtures.

The influence of small molecules on the main phase transition of dimyristoyl phosphatidylcholine was observed by high-sensitivity differential scanning calorimetry. The variation with temperature of the excess heat capacity is markedly affected by solid solution formation, which appears to be of frequent occurrence in solutions in lipid bilayers. The experimental results are in some cases in reasonable agreement with ideal solution theory.