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| 2. |
- Hjalte, Johanna, et al.
(författare)
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Modulating protein unfolding and refolding via the synergistic association of an anionic and a nonionic surfactant
- 2024
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797. ; 672, s. 244-255
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Tidskriftsartikel (refereegranskat)abstract
- Hypothesis: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation. Experiments: In this work, the behavior of three model proteins (human growth hormone, bovine serum albumin, and β-lactoglobulin) was investigated in the presence of the anionic surfactant sodium dodecylsulfate, the nonionic surfactant β-dodecylmaltoside, and mixtures of both surfactants. The transitions occurring to the proteins were determined using intrinsic fluorescence spectroscopy and far-UV circular dichroism. Based on these results, we developed a detailed interaction model for human growth hormone. Using nuclear magnetic resonance and contrast-variation small-angle neutron scattering, we studied the amino acid environment and the conformational state of the protein. Findings: The results demonstrate the key role of surfactant cooperation in defining the conformational state of the proteins, which can shift away or toward the folded state depending on the nonionic-to-ionic surfactant ratio. Dodecylmaltoside, initially a non-interacting surfactant, can unexpectedly associate with sodium dodecylsulfate-unfolded proteins to further impact their conformation at low nonionic-to-ionic surfactant ratio. When this ratio increases, the protein begins to retrieve the folded state. However, the native conformation cannot be fully recovered due to remnant surfactant molecules still adsorbed to the protein. This study demonstrates that the conformational landscape of the protein depends on a delicate interplay between the surfactants, ultimately controlled by the ratio between them, resulting in unpredictable changes in the protein conformation.
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| 3. |
- Kumar, Shailesh, et al.
(författare)
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Multifunctional Antioxidants : Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols
- 2016
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 55:11, s. 3729-3733
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Tidskriftsartikel (refereegranskat)abstract
- Regenerable, multifunctional ebselenol antioxidants were prepared that could quench peroxyl radicals more efficiently than -tocopherol. These compounds act as better mimics of the glutathione peroxidase enzymes than ebselen. Production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human mononuclear cells was considerably decreased upon exposure to the organoselenium compounds. At a concentration of 25m, the ebselenol derivatives showed minimal toxicity in pre-osteoblast MC3T3cells.
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| 4. |
- Lu, Xi, et al.
(författare)
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Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity
- 2017
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Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 6:13, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2 -induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.
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| 6. |
- Müller, Wenke, et al.
(författare)
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Impact of Additive Hydrophilicity on Mixed Dye-Nonionic Surfactant Micelles : Micelle Morphology and Dye Localization
- 2024
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Ingår i: Langmuir. - 0743-7463. ; 40:17, s. 8872-8885
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Tidskriftsartikel (refereegranskat)abstract
- The nonionic surfactant pentaethylene glycol-monododecylether C12E5 forms micelles in aqueous solutions with a lower critical solution temperature. This characteristic solution behavior of C12E5 is independent of the pH. Such micelles are used to solubilize a large variety of active guest molecules like for instance dyestuffs. An example is an acidic azo dye termed Blue used as a hair colorant. Depending on the pH, Blue gradually changes its hydrophilicity from the protonated BlueH at pH = 2 to the bivalent anion Blue2- at pH = 13 while keeping the shape and size of Blue essentially unchanged. These features of C12E5 and Blue offer the unique chance to investigate the sole impact of a tunable hydrophilicity of a guest molecule on the solution behavior of mixed micelles of the guest and C12E5. Accordingly, the present work establishes a phase diagram of Blue-C12E5 micelles and analyzes their morphology including the spatial distribution of Blue in the micelles as a function of the hydrophilicity of Blue. Small angle neutron scattering reveals the size and shape of the micelles, and detailed contrast matching of the C12E5 supported by 1H NMR with NOESY provided insight into the localization of Blue within the micelles as its hydrophilicity changes.
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| 7. |
- Poon, Jia-Fei, et al.
(författare)
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Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic Amines
- 2016
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 22:36, s. 12891-12903
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of a variety of aromatic amines carrying an ortho-alkyltelluro group is described. The new antioxidants quenched lipidperoxyl radicals much more efficiently than α-tocopherol and were regenerable by aqueous-phase N-acetylcysteine in a two-phase peroxidation system. The inhibition time for diaryl amine 9 b was four-fold longer than recorded with α-tocopherol. Thiol consumption in the aqueous phase was found to correlate inversely to the inhibition time and the availability of thiol is the limiting factor for the duration of antioxidant protection. The proposed mechanism for quenching of peroxyl radicals involves O-atom transfer from peroxyl to Te followed by H-atom transfer from amine to alkoxyl radical in a solvent cage.
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| 8. |
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| 9. |
- Poon, Jia-Fei, et al.
(författare)
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Azastilbenes : a cut-off to p38 MAPK inhibitors
- 2013
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Ingår i: Organic and biomolecular chemistry. - 1477-0520 .- 1477-0539. ; 11:27, s. 4526-4536
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38[small alpha] assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.
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| 10. |
- Poon, Jia-Fei, et al.
(författare)
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Azastilbenes: a cut-off to p38 MAPK inhibitors
- 2013
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Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 11:27, s. 4526-4536
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38α assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.
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