Amphiphilic polymers are increasingly applied in the detergent-free isolation and functional studies of membrane proteins. However, the carboxylate group present in the structure of many popular variants, such as styrene-maleic acid (SMA) copolymers, brings limitations in terms of polymer sensitivity to precipitation at acidic pH or in the presence of divalent metal cations. Herein, we addressed this problem by replacing carboxylate with the more acidic sulfonate groups. To this end, we synthesized a library of amphiphilic poly[styrene-co-(sodium 4-styrene sulfonate)] copolymers (termed SSS), differing in their molecular weight and overall polarity. Using model cell membranes (Jurkat), we identified two copolymer compositions (SSS-L30 and SSS-L36) that solubilized membranes to an extent similar to SMA. Interestingly, the density gradient ultracentrifugation/SDS-PAGE/Western blotting analysis of cell lysates revealed a distribution of studied membrane proteins in the gradient fractions that was different than for SMA-solubilized membranes. Importantly, unlike SMA, the SSS copolymers remained soluble at low pH and in the presence of Mg2+ ions. Additionally, the solubilization of DMPC liposomes by the lead materials was studied by turbidimetry, DLS, SEC, and high-resolution NMR, revealing, for SSS-L36, the formation of stable particles (nanodiscs), facilitated by the direct hydrophobic interaction of the copolymer phenyls with lipid acyl chains.

• Klíčová slova
• amphiphilic copolymer, cell membrane, membrane protein, solubilization, sulfonated polystyrene,
• Publikační typ
• časopisecké články MeSH

Dengue virus (DENV) causes 390 million infections per year. Infections can be asymptomatic or range from mild fever to severe haemorrhagic fever and shock syndrome. Currently, no effective antivirals or safe universal vaccine is available. In the present work we tested different gold nanoparticles (AuNP) coated with ligands ω-terminated with sugars bearing multiple sulfonate groups. We aimed to identify compounds with antiviral properties due to irreversible (virucidal) rather than reversible (virustatic) inhibition. The ligands varied in length, in number of sulfonated groups as well as their spatial orientation induced by the sugar head groups. We identified two candidates, a glucose- and a lactose-based ligand showing a low EC50 (effective concentration that inhibit 50% of the viral activity) for DENV-2 inhibition, moderate toxicity and a virucidal effect in hepatocytes with titre reduction of Median Tissue Culture Infectious Dose log10TCID50 2.5 and 3.1. Molecular docking simulations complemented the experimental findings suggesting a molecular rationale behind the binding between sulfonated head groups and DENV-2 envelope protein.

• MeSH
• antivirové látky chemie   farmakologie   MeSH
• buněčné linie MeSH
• buňky Hep G2 MeSH
• Cercopithecus aethiops MeSH
• dengue farmakoterapie   MeSH
• hepatocyty virologie   MeSH
• kovové nanočástice chemie   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• simulace molekulového dockingu MeSH
• Vero buňky MeSH
• virus dengue účinky léků   MeSH
• zlato chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antivirové látky MeSH
• ligandy MeSH
• zlato MeSH

In this work, novel proton-exchange membranes (PEMs) based on sulfonated poly(ether ether ketone) (SPEEK) and two-dimensional (2D) sulfonated niobium disulphide (S-NbS2) nanoflakes are synthesized by a solution-casting method and used in vanadium redox flow batteries (VRFBs). The NbS2 nanoflakes are produced by liquid-phase exfoliation of their bulk counterpart and chemically functionalized with terminal sulfonate groups to improve dimensional and chemical stabilities, proton conductivity (σ) and fuel barrier properties of the as-produced membranes. The addition of S-NbS2 nanoflakes to SPEEK decreases the vanadium ion permeability from 5.42 × 10-7 to 2.34 × 10-7 cm2 min-1. Meanwhile, it increases the membrane σ and selectivity up to 94.35 mS cm-2 and 40.32 × 104 S min cm-3, respectively. The cell assembled with the optimized membrane incorporating 2.5 wt% of S-NbS2 nanoflakes (SPEEK:2.5% S-NbS2) exhibits high efficiency metrics, i.e., coulombic efficiency between 98.7 and 99.0%, voltage efficiency between 90.2 and 73.2% and energy efficiency between 89.3 and 72.8% within the current density range of 100-300 mA cm-2, delivering a maximum power density of 0.83 W cm-2 at a current density of 870 mA cm-2. The SPEEK:2.5% S-NbS2 membrane-based VRFBs show a stable behavior over 200 cycles at 200 mA cm-2. This study opens up an effective avenue for the production of advanced SPEEK-based membranes for VRFBs.

• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Due to Albendazole's relatively low efficacy and bioavailability, Echinococcosis has proven a challenge to manage successfully, with several studies investigating ways to improve the outcome, mainly showing mixed results. We, therefore, aimed to evaluate whether Sulfonated Graphene Oxide (S-GO), as nanocarriers, could improve the mentioned outcome. METHODS: Echinococcus protoscoleces were divided into four groups based on the agent they received, which comprised control, S-GO, Albendazole, and Albendazole-loaded S-GO (S-GO-Albendazole). Then, the Bax and Bcl-2 gene expression levels and the number of surviving protoscoleces in each group were determined. RESULTS: Bax gene expression increased by 121% in the 50 μg/ml concentration of the S-GO-Albendazole, while Bcl-2 gene expression decreased by 64%. Moreover, S-GO-Albendazole was approximately 18% more effective at neutralizing protoscoleces than Albendazole and 14% and 31% more effective at improving the expression of the mentioned genes, respectively (p < 0.05). In addition, the number of surviving protoscoleces after exposure to the mentioned concentration reduced by approximately 99%. CONCLUSIONS: S-GO, despite not having significant lethality on protoscoleces, significantly increased the lethality of Albendazole and, therefore, is a suitable nanocarrier. However, we recommend conducting in vivo and clinical studies to more accurately determine this nanocomplex's potential and side effects.

• Publikační typ
• časopisecké články MeSH

Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine-mediated cleavage of trans-cyclooctene caged compounds (click-to-release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans-cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo-tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo-tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry.

• Klíčová slova
• bioorthogonal chemistry, cleavage reactions, click chemistry, click-to-release, tetrazines,
• MeSH
• click chemie MeSH
• fluorescenční barviva chemie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• molekulární struktura MeSH
• prekurzory léčiv chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorescenční barviva MeSH
• prekurzory léčiv MeSH

N-Sulfonated IAA was discovered as a novel auxin metabolite in Urtica where it is biosynthesized de novo utilizing inorganic sulfate. It showed no auxin activity in DR5::GUS assay, implying possible inactivation/storage mechanism. A novel auxin derivative, N-sulfoindole-3-acetic acid (IAA-N-SO3H, SIAA), was discovered in stinging nettle (Urtica dioica) among 116 sulfonated metabolites putatively identified by a semi-targeted UHPLC-QqTOF-MS analysis of 23 plant/algae/fungi species. These sulfometabolites were detected based on the presence of a neutral loss of sulfur trioxide, as indicated by the m/z difference of 79.9568 Da in the MS2 spectra. The structure of newly discovered SIAA was confirmed by synthesizing its standard and comparing retention time, m/z and MS2 spectrum with those of SIAA found in Urtica. To study its natural occurrence, 73 species in total were further analyzed by UHPLC-QqTOF-MS or targeted UHPLC-MS/MS method with a limit of detection of 244 fmol/g dry weight. However, SIAA was only detected in Urtica at a concentration of 13.906 ± 9.603 nmol/g dry weight. Its concentration was > 30 times higher than that of indole-3-acetic acid (IAA), and the SIAA/IAA ratio was further increased under different light conditions, especially in continuous blue light. In addition to SIAA, structurally similar metabolites, N-sulfoindole-3-lactic acid, 4-(sulfooxy)phenyllactic acid and 4-(sulfooxy)phenylacetic acid, were detected in Urtica for the first time. SIAA was biosynthesized from inorganic sulfate in seedlings, as confirmed by the incorporation of exogenous 34S-ammonium sulfate (1 mM and 10 mM). SIAA exhibited no auxin activity, as demonstrated by both the Arabidopsis DR5::GUS assay and the Arabidopsis phenotype analysis. Sulfonation of IAA may therefore be a mechanism for IAA deactivation and/or storage in Urtica, similar to sulfonation of the jasmonates in Arabidopsis.

• Klíčová slova
• N-Sulfoindole-3-acetic acid, Indole-3-acetic acid, Mass spectrometry, Metabolomics, Phytohormone, Sulfonated,
• MeSH
• Arabidopsis metabolismus   MeSH
• kyseliny indoloctové * metabolismus   MeSH
• regulátory růstu rostlin metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Urtica dioica metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• indoleacetic acid MeSH Prohlížeč
• kyseliny indoloctové * MeSH
• regulátory růstu rostlin MeSH

Despite intense research in the field of aqueous organic redox flow batteries, low molecular stability of electroactive compounds limits further commercialization. Additionally, currently used methods typically cannot differentiate between individual capacity fade mechanisms, such as degradation of electroactive compound and its cross-over through the membrane. We present a more complex method for in situ evaluation of (electro)chemical stability of electrolytes using a flow electrolyser and a double half-cell including permeation measurements of electrolyte cross-over through a membrane by a UV-VIS spectrometer. The method is employed to study (electro)chemical stability of acidic negolyte based on an anthraquinone sulfonation mixture containing mainly 2,6- and 2,7-anthraquinone disulfonic acid isomers, which can be directly used as an RFB negolyte. The effect of electrolyte state of charge (SoC), current load and operating temperature on electrolyte stability is tested. The results show enhanced capacity decay for fully charged electrolyte (0.9 and 2.45% per day at 20 °C and 40 °C, respectively) while very good stability is observed at 50% SoC and lower, even at 40 °C and under current load (0.02% per day). HPLC analysis conformed deep degradation of AQ derivatives connected with the loss of aromaticity. The developed method can be adopted for stability evaluation of electrolytes of various organic and inorganic RFB chemistries.

• Klíčová slova
• anthraquinone disulfonic acid, aqueous organic electrolyte, capacity decay, electrolyte cross-over, redox flow battery,
• Publikační typ
• časopisecké články MeSH

The RNA editing core complex (RECC) catalyzes mitochondrial U-insertion/deletion mRNA editing in trypanosomatid flagellates. Some naphthalene-based sulfonated compounds, such as C35 and MrB, competitively inhibit the auto-adenylylation activity of an essential RECC enzyme, kinetoplastid RNA editing ligase 1 (KREL1), required for the final step in editing. Previous studies revealed the ability of these compounds to interfere with the interaction between the editosome and its RNA substrates, consequently affecting all catalytic activities that comprise RNA editing. This observation implicates a critical function for the affected RNA binding proteins in RNA editing. In this study, using the inhibitory compounds, we analyzed the composition and editing activities of functional editosomes and identified the mitochondrial RNA binding proteins 1 and 2 (MRP1/2) as their preferred targets. While the MRP1/2 heterotetramer complex is known to bind guide RNA and promote annealing to its cognate pre-edited mRNA, its role in RNA editing remained enigmatic. We show that the compounds affect the association between the RECC and MRP1/2 heterotetramer. Furthermore, RECC purified post-treatment with these compounds exhibit compromised in vitro RNA editing activity that, remarkably, recovers upon the addition of recombinant MRP1/2 proteins. This work provides experimental evidence that the MRP1/2 heterotetramer is required for in vitro RNA editing activity and substantiates the hypothesized role of these proteins in presenting the RNA duplex to the catalytic complex in the initial steps of RNA editing.

• Klíčová slova
• MRP1/2, RNA editing, RNA editing initiation, RNA-binding protein, inhibitor, trypanosome,
• MeSH
• editace RNA účinky léků   genetika   MeSH
• guide RNA, Kinetoplastida účinky léků   MeSH
• ligasy antagonisté a inhibitory   MeSH
• messenger RNA genetika   MeSH
• mitochondriální proteiny genetika   MeSH
• mitochondrie účinky léků   genetika   MeSH
• proteiny vázající RNA genetika   MeSH
• protozoální proteiny genetika   MeSH
• rekombinantní proteiny genetika   MeSH
• RNA mitochondriální genetika   MeSH
• RNA protozoální genetika   MeSH
• Trypanosoma brucei brucei účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gBP21 protein, Trypanosoma brucei MeSH Prohlížeč
• gBP25 protein, Trypanosoma brucei MeSH Prohlížeč
• guide RNA, Kinetoplastida MeSH
• ligasy MeSH
• messenger RNA MeSH
• mitochondriální proteiny MeSH
• proteiny vázající RNA MeSH
• protozoální proteiny MeSH
• rekombinantní proteiny MeSH
• RNA mitochondriální MeSH
• RNA protozoální MeSH

Herein, we report the first chiral phosphoric acid (CPA)-catalyzed asymmetric addition of α-fluoro(phenylsulfonyl)methane (FSM) derivatives to in situ generated cyclic N-acyliminium. This process enables metal-free expeditious access to sulfone and fluorine incorporating contiguous all substituted quaternary stereocenters ingrained in biorelevant isoindolinones in excellent stereoselectivities (up to 99% ee and up to 50 : 1 dr).

• MeSH
• katalýza MeSH
• methan * MeSH
• stereoizomerie MeSH
• sulfony * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• methan * MeSH
• sulfony * MeSH

• Klíčová slova
• DERMATITIS HERPETIFORMIS/therapy *, SULFONES/therapy *,
• MeSH
• dermatitis herpetiformis terapie   MeSH
• sulfony terapie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• sulfony MeSH