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排序方式: 共有239条查询结果,搜索用时 62 毫秒
1.
Dr. Rainer Müller Dr. Mevlut Citir Dr. Sebastian Hauke Prof. Dr. Carsten Schultz 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(2):384-389
Phosphatidylinositol (PI) is the biosynthetic precursor for seven phosphoinositides, important signaling lipids in cells. A membrane-permeant caged PI derivative featuring a photo-removable coumarinyl group masking the negative charge of the phosphate, as well as two enzymatically removable butyrate esters for increased lipophilicity and for preventing phosphate migration, were synthesized. Rapid cell entry and cellular labeling in fixed cells was demonstrated by a photo-cross-linkable diazirine followed by attachment of a fluorophore through click chemistry. Using this technique, we found that the multifunctional caged PI derivative resided predominantly at internal membranes but rapidly changed to the plasma membrane after uncaging. Accordingly, a preliminary proteomic analysis of the lipid–protein conjugates revealed that the two major PI transport proteins PITPα and β were prime targets of the photo-cross-linked PI derivative. 相似文献
2.
Valentina Bleve Christian Schäfer Dr. Paola Franchi Dr. Serena Silvi Prof. Dr. Elisabetta Mezzina Prof. Dr. Alberto Credi Prof. Marco Lucarini 《ChemistryOpen》2015,4(1):2-21
An acid–base switchable molecular shuttle based on a [2]rotaxane, incorporating stable radical units in both the ring and dumbbell components, is reported. The [2]rotaxane comprises a dibenzo[24]crown-8 ring (DB24C8) interlocked with a dumbbell component that possesses a dialkylammonium (NH2+) and a 4,4′-bipyridinium (BPY2+) recognition site. Deprotonation of the rotaxane NH2+ centers effects a quantitative displacement of the DB24C8 macroring to the BPY2+ recognition site, a process that can be reversed by acid treatment. Interaction between stable 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals connected to the ring and dumbbell components could be switched between noncoupled (three-line electron paramagnetic resonance (EPR) spectrum) and coupled (five-line EPR spectrum) upon displacement of the spin-labelled DB24C8 macroring. The complete base- and acid-induced switching cycle of the EPR pattern was repeated six times without an appreciable loss of signal, highlighting the reversibility of the process. Hence, this molecular machine is capable of switching on/off magnetic interactions by chemically driven reversible mechanical effects. A system of this kind represents an initial step towards a new generation of nanoscale magnetic switches that may be of interest for a variety of applications. 相似文献
3.
Marco Verona Sara Rubagotti Stefania Croci Sophia Sarpaki Francesca Borgna Marianna Tosato Elisa Vettorato Giovanni Marzaro Francesca Mastrotto Mattia Asti 《Molecules (Basel, Switzerland)》2021,26(4)
The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [111In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys. 相似文献
4.
Mattes Holsten Sarah Feierabend Dr. Sven M. Elbert Dr. Frank Rominger Dr. Thomas Oeser Prof. Dr. Michael Mastalerz 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(36):9383-9390
One of the most applied reaction types to synthesize shape-persistent organic cage compounds is the imine condensation reaction and it is assumed that the formed cages are thermodynamically controlled products due to the reversibility of the imine condensation. However, most of the synthesized imine cages reported are formed as precipitate from the reaction mixture and therefore rather may be kinetically controlled products. There are even examples in literature, where resulting cages are not soluble at all in common organic solvents to characterize or study their formation by NMR spectroscopy in solution. Here, a triptycene triamine containing three solubilizing n-hexyloxy chains has been used to synthesize soluble congeners of prior insoluble cages. This allowed us to study the formation as well as the reversibility of cage formation in solution by investigating exchange of building blocks between the cages and deuterated derivatives thereof. 相似文献
5.
Dr. Marion Daniel-Bertrand Sébastien Garcia-Argote Dr. Alberto Palazzolo Dr. Irene Mustieles Marin Dr. Pier-Francesco Fazzini Dr. Simon Tricard Dr. Bruno Chaudret Dr. Volker Derdau Dr. Sophie Feuillastre Dr. Grégory Pieters 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(47):21300-21306
Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late-stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air-stable iridium precatalyst [Ir(COD)(OMe)]2 is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa-/thia-zoles, thiophene, but also electron-rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles. 相似文献
6.
J. E. Komosiński 《Isotopes in environmental and health studies》2013,49(5):199-201
Studies on the workability of precise seeders by means of labelling methods has been possible due to the solution of the following problems: labelling of seeds, radiation collimation of labelled seeds being sown, elaboration of measuring and registering systems as well as processing systems of a measuring signal. The developed method allows for precise, quick and fully objective evaluation of the studied seeders to be done under natural conditions. 相似文献
7.
8.
Zur Vervollkommung der strahlenchemischen Technologie für die Herstellung einiger für die Industrie wichtiger silizium-organischer Monomere und zur Durchführung von Forschungs-arbeiten auf diesem Gebiet wurde eine Pilot-Anlage unter Verwendung des Elektronenbeschleunigers EU-0,4 geschaffen, der im Physikalisch-chemischen Forschungsinstitut ?L. J. Karpow“ auf der Grundlago des Rōntgendefektoskopie-Gerātes RUP-400-5 entwickelt wurde. 相似文献
9.
Dr. Nan Chen Dr. Yuan Liu Yuanpei Li Prof. Dr. Chu Wang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(37):16203-16209
Protein 4′-phosphopantetheinylation is an essential post-translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid biosynthesis and folate metabolism, as well as β-alanine activation. To explore existing and new substrates of 4′-phosphopantetheinylation in mammalian proteomes, we designed and synthesized a series of new pantetheine analogue probes, enabling effective metabolic labelling of 4′-phosphopantetheinylated proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4′-phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4′-phosphopantetheinylation site in the protein of mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2). 相似文献
10.
Isabel V. L. Wilkinson Kelly J. Perkins Hannah Dugdale Lee Moir Aini Vuorinen Maria Chatzopoulou Sarah E. Squire Sebastian Monecke Alexander Lomow Marcus Geese Philip D. Charles Peter Burch Jonathan M. Tinsley Graham M. Wynne Stephen G. Davies Francis X. Wilson Fraydoon Rastinejad Shabaz Mohammed Kay E. Davies Angela J. Russell 《Angewandte Chemie (International ed. in English)》2020,59(6):2420-2428
Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies. 相似文献