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The effect of hyperphosphorylation on the structural properties and conformational stability of bovine tau-protein was studied by means of circular dichroism and fluorescence lifetime techniques. Normal protein contains unusual secondary structure elements: extended left-handed helices. The structure of this protein was assumed to be of a'tadpole' type^a globular Cterminal part with a long and rigid tail included in the extended left-handed helix. Either a decrease or an increase of pH induceddoi:10.1016/s0014-5793(98)01303-9 pmid:9849869 fatcat:7ncivqtxafeu7dpt73lc5v6t44
more »... nly minor changes of the normal tau-protein surface. Hyperphosphorylation affected the extended part of the protein molecule; the decrease of pH in this case induced considerable structural rearrangements, and the conformation of the Cterminal part of the protein molecule was transformed into a molten globule-like state. z 1998 Federation of European Biochemical Societies.
Dopamine is a neurotransmitter of great physiological relevance. Disorders in dopaminergic signal transduction are associated with psychiatric and neurological pathologies such as Parkinson's disease, schizophrenia and substance abuse. Therefore, a detailed understanding of dopaminergic neurotransmission may provide access to novel therapeutic strategies for the treatment of these diseases. Caged compounds with photoremovable groups represent molecular tools to investigate a biological targetdoi:10.1038/s41598-020-57770-9 pmid:31965029 pmcid:PMC6972920 fatcat:wt4hfycucnbnnikzh4ft62772e
more »... th high spatiotemporal resolution. Based on the crystal structure of the D3 receptor in complex with eticlopride, we have developed caged D2/D3 receptor ligands by rational design. We initially found that eticlopride, a widely used D2/D3 receptor antagonist, was photolabile and therefore is not suitable for caging. Subtle structural modification of the pharmacophore led us to the photostable antagonist dechloroeticlopride, which was chemically transformed into caged ligands. Among those, the 2-nitrobenzyl derivative 4 (MG307) showed excellent photochemical stability, pharmacological behavior and decaging properties when interacting with dopamine receptor-expressing cells.
Human ether a © go-go potassium channel 2 (hEAG2) was cloned and its properties were compared with the previously characterized isoform hEAG1. In the Xenopus oocyte expression system the time course of activation was about four times slower and the voltage required for half-maximal subunit activation was about 10 mV greater for hEAG2 channels. However, its voltage dependence was smaller and, therefore, hEAG2 channels start to open at more negative voltages than hEAG1. Coexpression of bothdoi:10.1016/s0014-5793(02)02365-7 pmid:11943152 fatcat:r7llxvv4a5frressbnnzg7iiue
more »... ms and kinetic analysis of the resulting currents indicated that they can form heteromeric channel complexes in which the slow activation phenotype of hEAG2 is dominant. Upon expression in mammalian cells, quinidine blocked hEAG1 channels (IC 50 1.4 W WM) more potently than hEAG2 channels (IC 50 152 W WM), thus providing a useful tool for the functional distinction between hEAG1 and hEAG2 potassium channels. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
General: All reactions were carried out in air unless otherwise indicated. Doxycycline hydrate, tetracycline hydrochloride and tetracycline hydrate for chemical synthesis were aquired from Heumann Pharma, Synopharm GmbH and Fluka, respectively. All chemicals were used as purchased. Doxycycline and anhydrotetrycycline for biological testing were purchased as hydrochlorides from Sigma and Acros Organics (Geel, Belgium), respectively. D-luciferin and coelenterazine were purchased from P.J.K.doi:10.1002/cbic.200600226 pmid:16871602 fatcat:gnouaa5i2ndopkgtlr7pd5pt6e
more »... blittersdorf, Germany). 1 H and 13 C NMR spectra were recorded at 300 K on a Bruker Avance 360 (360 MHz) or a Bruker Avance 600 (600 MHz). LC-MS analyses were performed with an Agilent 1100 HPLC combined with a Bruker Esquire 2000 mass spectrometer. HR-EIMS spectra were recorded on a Jeol GCmateII. Preparative HPLC was performed on an Agilent 1100 system using RP-18 colums (Agilent Zorbax 300SB, 7µm or CS-Chromatographie Eurospher C-18, 7µm) and CH 3 CN/ 0.1% aq. TFA or MeOH/0,1% aq. TFA as solvent systems. MPLC separation was performed on a Büchi Chromatography System (binary pump B-688, gradient former B-687 and glass columns B-685) with UV detection at 254 nm using Europrep 60-30 C18 (Eurochrom®, Knauer) RP silica gel and CH 3 CN / 0.1 % aq. TFA as a solvent system. In all cases HPLC grade solvents were used.
Based on the lead molecule FAUC 113, a series of di-and trisubstituted pyrazolo[1,5-a]pyridine derivatives was synthesized and investigated for their dopamine receptor binding profile. The carbonitrile 11a (FAUC 327) showed excellent pharmacological properties combining high D4 affinity (K i =1.5 nM) and selectivity with significant intrinsic activity (31%) in low nanomolar concentrations (EC 50 =1.5 nM). #doi:10.1016/s0960-894x(01)00814-9 pmid:11844688 fatcat:jydpndwcjzhpxacpoikfchos64
Activation of inflammatory cells is central to the pathogenesis of autoimmune demyelinating diseases of the peripheral nervous system. The novel chimeric compound quinpramine-generated from imipramine and quinacrine-redistributes cholesterol rich membrane domains to intracellular compartments. We studied the immunological and clinical effects of quinpramine in myelin homogenate induced Lewis rat experimental autoimmune neuritis (EAN), a model system for acute human inflammatory neuropathies,doi:10.1371/journal.pone.0021223 pmid:21698177 pmcid:PMC3116892 fatcat:yd4asbiymfeorlsichyfi56rei
more »... h as the Guillain-Barré syndrome. EAN animals develop paresis of all limbs due to autoimmune inflammation of peripheral nerves. Quinpramine treatment ameliorated clinical disease severity of EAN and infiltration of macrophages into peripheral nerves. It reduced expression of MHC class II molecules on antigen presenting cells and antigen specific T cell proliferation both in vitro and in vivo. Quinpramine exerted its anti-proliferatory effect on antigen presenting cells, but not on responder T cells. Our data suggest that quinpramine represents a candidate pharmaceutical for inflammatory neuropathies.
Two fluoroethoxy substituted derivatives, namely 2-[4-(2-(2-fluoroethoxy)phenyl)piperazin-l-ylmethyl]indole-5-carbonitrile (5a) and 2-[4-(4-(2-fluoroethoxy)-phenyl) piperazin-l-ylmethyl]indole-5-carbonitrile (5b) were synthesized as analogs of the selective D4 receptor ligand 2-[4-(4-fluorophenyl)piperazin-l-ylmethyl]indole-5-carbonitrile (FADC 316). In vitro characterization using CRO-cells expressing different dopamine receptor subtypes gave K; values of 2.1 (5a) and 9.9 nM (5b) for thedoi:10.1002/jlcr.1026 fatcat:6iig6xa4qnbvpj2aw725yytmry
more »... ne D4 subtype and displayed a 420-fold D4-selectivity over D2 receptors for 5b. The para-fluoroethoxy substituted candidate 5b revealed substantially reduced (Xl and serotoninergic binding affinities in comparison to the ortho-fluoroethoxy substituted compound. In order to provide potential positron emission tomography (PET) imaging probes for the dopamine D4 receptor, 18F-labelling conditions using C 8 F]fluoroethyl tosylate were optimized and led to radiochemical yields of 81 ± 5% ([ 18 F]5a) and 47 ± 4% ([ 18 F]5b) (n = 3, decay-corrected and referred to labelling agent), respectively. Thus, 18F-fluoroethylation favourably at the para position of the phenylpiperazine moiety of the 5-cyano-indole framework proved to be tolerated by D4 receptors and could also be applied to alternative scaffolds in order to develop D4 radioligand candidates for PET with improved D4 receptor affinity and selectivity.
Folding & design
It is known that nonnative states of protein molecules can exist in living cells and can be involved in a number of physiological processes. It has also been established that the membrane surface can be responsible for the partial denaturation of proteins due to negative charges on it. The local decrease in the effective dielectric constant of water near the organic surface has been suggested to be an additional driving force for protein denaturation in the membrane field, but data to confirmdoi:10.1016/s1359-0278(97)00023-0 pmid:9218954 fatcat:jo4wa7udardshafijevhtb3xt4
more »... is suggestion were lacking. Results: Conformational transitions induced in ␤-lactoglobulin by methanol, ethanol, isopropanol, dimethylformamide and dioxane were studied by near and far UV circular dichroism, steady-state tryptophan fluorescence and fluorescence decay of 8-anilinonaphthalene-1-sulfonate (8-ANS). The existence of at least two noncoinciding cooperative transitions has been established in all solvent systems studied. The first of these transitions describes the disruption of rigid tertiary structure in protein molecules, while the second reflects the formation of an expanded helical conformation typical of proteins in concentrated organic solvents. This means that the organic solvents provoke the formation of a denatured intermediate state with pronounced secondary structure and native-like compactness. We show that the positions of maxima in f I versus dielectric constant dependence virtually coincide for all five solvent systems studied. Conclusions: The decrease in the dielectric constant of the solvent induces in ␤-lactoglobulin an equilibrium intermediate state. This state, being denatured, is relatively compact and has pronounced secondary structure and high affinity for the hydrophobic fluorescent probe 8-ANS, i.e. possesses all the properties of the molten globule intermediate state. Addresses:
Löber, Peter Gmeiner, Teja W Grömer and Christian P Müller in Journal of Psychopharmacology ... in psychotic-like rats by Taygun C Uzuneser, Eva-Maria Weiss, Jana Dahlmanns, Liubov S Kalinichenko, Davide Amato, Johannes Kornhuber, Christian Alzheimer, Jan Hellmann, Jonas Kaindl, Harald Hübner, Stefan ...doi:10.25384/sage.13337216.v1 fatcat:vjsapndrffbk7iqsxu7njbpufy
Economic Development and Cultural Change
Lober, “International Ecotourism and the Valuation of Tropical Rainforests in Costa Rica,” Journal of Environmental Management 47 (1996): 1-10; Lisa C. Chase, David R. Lee, William D. ... Stefan Géssling, “Ecotourism: A Means to Safeguard Biodiversity and Eco- system Functions,” Ecological Economics 29 (1999): 303-20; Sven Wunder, “Eco- tourism and Economic Incentives: An Empirical Approach ...
et al. 1998; Erickson and Stefan, 2000) . ... The narrowest average CI's (2.7ºC, 2.9ºC) occurred at Lober River and Opatawicki River, sites with moderate NSC's (0.87,0.83, respectively). ...doi:10.1061/(asce)0733-9372(2005)131:1(139) fatcat:kmyveq24mzgqjbjfrclb52bdia
Stefan Böschen beleuchtete in seinem Beitrag die regulative Dimension des Verhältnisses von Politik und Wissenschaft am Beispiel der Ökologischen Chemie. ... Dass Wissen auch eine Kategorie zur Analyse von Policy-Instrumenten sein könne, versuchte Sonja Löber in ihrem Vortrag am Beispiel der Umweltpolitik vorzustellen. ...doi:10.14512/tatup.19.3.116 fatcat:qzqq3qd6avau3fhk5j2yczufam
Anmeldelse af Stefan Iversen: Den uhyggelige fortælling – unaturlig narratologi og Johannes V. Jensens tidlige forfatterskab. Aarhus: Aarhus Universitetsforlag 2018, 374 sider, 299 kr. ... Men da han løber tør for analyseredskaber, henlaegges den. ...doi:10.7146/pas.v33i80.111730 fatcat:ml2vkqgkbfg5hp5cyv6ix2snwm
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