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21.
Julia Post Vanessa Kogel Anja Schaffrath Philipp Lohmann N. Jon Shah Karl-Josef Langen Dieter Willbold Antje Willuweit Janine Kutzsche 《Molecules (Basel, Switzerland)》2021,26(6)
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by selective neuronal death in the brain stem and spinal cord. The cause is unknown, but an increasing amount of evidence has firmly certified that neuroinflammation plays a key role in ALS pathogenesis. Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and has been implicated as driver of disease progression. Here, we describe a treatment study demonstrating the therapeutic potential of a tandem version of the well-known all-d-peptide RD2 (RD2RD2) in a transgenic mouse model of ALS (SOD1*G93A). Mice were treated intraperitoneally for four weeks with RD2RD2 vs. placebo. SOD1*G93A mice were tested longitudinally during treatment in various behavioural and motor coordination tests. Brain and spinal cord samples were investigated immunohistochemically for gliosis and neurodegeneration. RD2RD2 treatment in SOD1*G93A mice resulted not only in a reduction of activated astrocytes and microglia in both the brain stem and lumbar spinal cord, but also in a rescue of neurons in the motor cortex. RD2RD2 treatment was able to slow progression of the disease phenotype, especially the motor deficits, to an extent that during the four weeks treatment duration, no significant progression was observed in any of the motor experiments. Based on the presented results, we conclude that RD2RD2 is a potential therapeutic candidate against ALS. 相似文献
22.
Watzke A Brunsveld L Durek T Alexandrov K Rak A Goody RS Waldmann H 《Organic & biomolecular chemistry》2005,3(7):1157-1164
Rab/Ypt guanosine triphosphatases (GTPases) represent a family of key membrane traffic regulators in eukaryotic cells. For their function Rab/Ypt proteins require double modification with two covalently bound geranylgeranyl lipid moieties at the C-terminus. Generally, prenylated proteins are very difficult to obtain by recombinant or enzymatic methods. We generated prenylated RabGTPases using a combination of chemical synthesis and protein engineering. This semi-synthesis depends largely on the availability of functionalized prenylated peptides corresponding to the proteins' native structure or modifications. We developed solution phase and solid phase strategies for the generation of peptides corresponding to the prenylated C-terminus of Rab7 GTPase in preparative amounts enabling us to crystallize the mono-prenylated Ypt1:RabGDI complex. The structure of the complex provides a structural basis for the ability of RabGDI to inhibit the release of nucleotide by Rab proteins and a molecular basis for understanding a RabGDI mutant that causes mental retardation in humans. 相似文献
23.
Giraud N Blackledge M Goldman M Böckmann A Lesage A Penin F Emsley L 《Journal of the American Chemical Society》2005,127(51):18190-18201
A detailed analysis of nitrogen-15 longitudinal relaxation times in microcrystalline proteins is presented. A theoretical model to quantitatively interpret relaxation times is developed in terms of motional amplitude and characteristic time scale. Different averaging schemes are examined in order to propose an analysis of relaxation curves that takes into account the specificity of MAS experiments. In particular, it is shown that magic angle spinning averages the relaxation rate experienced by a single spin over one rotor period, resulting in individual relaxation curves that are dependent on the orientation of their corresponding carousel with respect to the rotor axis. Powder averaging thus leads to a nonexponential behavior in the observed decay curves. We extract dynamic information from experimental decay curves, using a diffusion in a cone model. We apply this study to the analysis of spin-lattice relaxation rates of the microcrystalline protein Crh at two different fields and determine differential dynamic parameters for several residues in the protein. 相似文献
24.
Tolonen A Uusitalo J Hohtola A Jalonen J 《Rapid communications in mass spectrometry : RCM》2002,16(5):396-402
Hypericum perforatum L. (St. John's Wort) has long been known as a medicinal plant, and has been used for the treatment of depression and neuralgic disorders. Its main active constituents are believed to be a naphthodianthrone, hypericin, and a phloroglucinol, hyperforin. A sensitive high performance liquid chromatography (HPLC)/electrospray tandem mass spectrometric method for fast simultaneous determination of six major naphthodianthrones and phloroglucinols of Hypericum perforatum extract has been developed. The method, based on multiple dissociation reaction monitoring (MRM), allows the analysis of hypericin, protohypericin, pseudohypericin, protopseudo-hypericin, hyperforin and adhyperforin from the extract in less than 5 min. Good linearity over the range 0.1-1000 ng/mL for hyperforin and 2-500 ng/mL for hypericin was observed. Intra-assay accuracy and precision varied from 2 to 19% within these ranges. Lower levels of quantitation for hyperforin were 0.5 ng/mL and 2 ng/mL for hypericin. 相似文献
25.
Mathilde Briday Franois Hall Lauriane Lecoq Sylvie Radix Juliette Martin Roland Montserret Marie Dujardin Marie-Laure Fogeron Michael Nassal Beat H. Meier Thierry Lomberget Anja Bckmann 《Chemical science》2022,13(30):8840
Hepatitis B virus (HBV) is a small enveloped retrotranscribing DNA virus and an important human pathogen. Its capsid-forming core protein (Cp) features a hydrophobic pocket proposed to be central notably in capsid envelopment. Indeed, mutations in and around this pocket can profoundly modulate, and even abolish, secretion of enveloped virions. We have recently shown that Triton X-100, a detergent used during Cp purification, binds to the hydrophobic pocket with micromolar affinity. We here performed pharmacomodulation of pocket binders through systematic modifications of the three distinct chemical moieties composing the Triton X-100 molecule. Using NMR and ITC, we found that the flat aromatic moiety is essential for binding, while the number of atoms of the aliphatic chain modulates binding affinity. The hydrophilic tail, in contrast, is highly tolerant to changes in both length and type. Our data provide essential information for designing a new class of HBV antivirals targeting capsid–envelope interactions.Small-molecule binding to the Hepatitis B virus core protein hydrophobic pocket, a possible strategy for targeting viral particle assembly. 相似文献
26.
N. Ahmad C. Nanjundayya W. G. Chace M. A. Ssobolew M. M. Tschilikin A. T. Iwanowa F. Kalmanowitsch A. Kolotyrewa C. F. Cross E. J. Bevan A. Eavenson J. W. Creely J. H. Skinkle O. Viertel A. J. Hall W. N. Udalskaja D. A. Clibbens A. H. Little Karin Schulze S. M. Edelstein E. Lindemann F. Schütz W. Klauditz P. Winterfeld F. H. Guernsay L. T. Howells F. Schroeder R. Finlay G. Hasse Niederhauser H. Ris R. D. Nutting W. Lesnianski F. Fabrowicz und Coch 《Fresenius' Journal of Analytical Chemistry》1938,115(1-2):51-57
Ohne Zusammenfassung 相似文献
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29.
Martin Scherer Patrick Scheibe Jérôme Schoenhentz Anja Hoffmann-Röder Rudolf Zentel 《Colloid and polymer science》2014,292(8):1803-1815
This paper deals with pattern formation in Langmuir monolayers of two sets of lipid mixtures that include (1) a fluorinated lipid for phase separation, (2) a polymerizable lipid for stabilization of the patterned structure, and (3) a unit for the presentation of biological recognition units. Differences in the distribution of these functionalities allow a polymerization of dispersed or continuous phase and a placement of the recognition units in crystalline or solid analogue phase. Also, a ternary mixture including a lipid modified with the tandem repeat domain of MUC1 plus a TN-antigen was studied. Based on the biphasic pattern obtained (starlike crystals of up to 50 μm with a fine structure of some micrometers), we also verified the potential of the laterally patterned monolayer to stimulate the immune system (quartz crystal microbalance). The second set of lipids combines a highly fluorinated itaconic ester (polymerizable unit) with the natural phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine. 相似文献
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