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61.
Anna Schüller Daniel Matzner Dr. Christina E. Lünse Prof. Dr. Valentin Wittmann Dr. Catherine Schumacher Sandra Unsleber Prof. Dr. Heike Brötz‐Oesterhelt Prof. Dr. Christoph Mayer Prof. Dr. Gabriele Bierbaum Prof. Dr. Günter Mayer 《Chembiochem : a European journal of chemical biology》2017,18(5):435-440
The ever‐growing number of pathogenic bacteria resistant to treatment with antibiotics call for the development of novel compounds with as‐yet unexplored modes of action. Here, we demonstrate the in vivo antibacterial activity of carba‐α‐d ‐glucosamine (CGlcN). In this mode of action study, we provide evidence that CGlcN‐mediated growth inhibition is due to glmS ribozyme activation, and we demonstrate that CGlcN hijacks an endogenous activation pathway, hence utilizing a prodrug mechanism. This is the first report describing antibacterial activity mediated by activating the self‐cleaving properties of a ribozyme. Our results open the path towards a compound class with an entirely novel and distinct molecular mechanism. 相似文献
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The knowledge of the cellular molar concentration of a drug is an extremely important parameter for the discussion and interpretation of its efficacy and bioavailability. Concerning metal complexes, electrothermal atomic absorption spectroscopy (ETAAS) offers a valuable analytical tool. However, matrix effects often hamper proper quantification of the metal concentration in biological tissues. This paper describes the development of an ETAAS method for the quantification of the molar gold concentration in HT-29 colon carcinoma cells. ETAAS analytical conditions were optimised and a factor was developed which allows the calculation of the molar cellular gold concentration from the measured gold per cellular biomass value. The method was used to quantify the gold content in HT-29 cells after exposure to the gold drug auranofin. Results indicated a strong cellular uptake of auranofin (compared to other metal anticancer drugs), which significantly correlated with the antiproliferative effects triggered by this agent. 相似文献
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Product Engineering in the Case of Extruded Instant Powders . Starch based instant powders are usually produced by cooking/gelatinizing in an excess of water with subsequent drying and milling. Important product attributes are the specific weight and the instant properties of the powder, as well as the taste, the viscosity, and the mouth-feel of the reconstituted gel. Cooking extrusion is an alternative energy saving process. Process development usually takes a long time and proves expensive due to the large number of different process parameters and their possible combinations. For two exemplary products it is demonstrated how the screw configuration and the target range of process parameters can be defined by statistical trial design. Final optimization (?fine tuning”?) and scale-up assure efficient process design according to product needs. 相似文献
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Max Braune Nico Scherf Claudia Heine Katja Sygnecka Thanigaimalai Pillaiyar Chiara Parravicini Bernd Heimrich Maria P. Abbracchio Christa E. Müller Heike Franke 《International journal of molecular sciences》2021,22(21)
Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growth-promoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration. 相似文献
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Heike Keutel Helmar Grls Wolfgang Poppitz Adelheid Schütz E.‐G. Jger 《Advanced Synthesis \u0026amp; Catalysis》1999,341(8):785-791
Condensation products of L‐histidine with the 3‐oxoenolethers diethyl‐ethoxymethylene‐malonate ( 1 ) and ethyl‐ethoxymethylene‐cyanoacetate ( 2 ) react with copper(II) as di‐anionic ligands to give neutral 1:1 complexes Cu‐ His1 and Cu‐ His2 . Both complexes crystallize as oligonuclear units, even from strongly donating solvents like N‐methylimidazole (Meim) (Cu‐ His1 ) and pyridine (Cu‐ His2 ). X‐ray structure analyses show supramolecular structures, formed of two (Cu‐ His1 ) or four (Cu‐ His2 ) formula units of the complex, which arrange to macrocycles by means of intermolecular coordination of the imidazole‐N. Strong H‐bridges result in a face‐to‐face orientation of the hydrophilic sites of two great rings. ESI‐MS investigations in pyridine solution give evidence for the existence of dimeric, tetrameric and – in case of Cu‐ His2 – trimeric units, besides the monomeric adducts with one pyridine. In contrast to the dimeric or tetrameric (“cubane‐like”) copper(II) complexes of amino alcohols and their β‐ketoenamines, the complexes Cu‐ His1 and Cu‐ His2 show no significant spin coupling from room temperature down to 4 K. The complexes Cu‐ His1 and Cu‐ His2 give no electrochemically reversible CuII/I reduction in pyridine. However, the isolation of a stable diamagnetic copper(I) complex of the methylester derivative, CuI‐ HisMe1 , supports the assumption, that similar histidine‐derived copper complexes should display reversible redox behaviour and catalytic activity in reactions with O2. 相似文献
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