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101.
Ania Alik Chafiaa Bouguechtouli Manon Julien Dr. Wolfgang Bermel Rania Ghouil Dr. Sophie Zinn-Justin Dr. Francois-Xavier Theillet 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(26):10497-10501
Abundant phosphorylation events control the activity of nuclear proteins involved in gene regulation and DNA repair. These occur mostly on disordered regions of proteins, which often contain multiple phosphosites. Comprehensive and quantitative monitoring of phosphorylation reactions is theoretically achievable at a residue-specific level using 1H-15N NMR spectroscopy, but is often limited by low signal-to-noise at pH>7 and T>293 K. We have developed an improved 13Cα-13CO correlation NMR experiment that works equally at any pH or temperature, that is, also under conditions at which kinases are active. This allows us to obtain atomic-resolution information in physiological conditions down to 25 μm . We demonstrate the potential of this approach by monitoring phosphorylation reactions, in the presence of purified kinases or in cell extracts, on a range of previously problematic targets, namely Mdm2, BRCA2, and Oct4. 相似文献
102.
《Operations Research Letters》2020,48(5):552-557
Most of the existing models for Age of Information (AoI) are limited to cases where data generation is according to Poisson process and/or Exponential distribution processing times. Those that consider more general distributions have results only for the first moment of AoI. Discrete time systems for AoI are now receiving attention. In this paper the system is modelled as a discrete time Markov chain and matrix-geometric method is used to obtain the probability mass function of the AoI. 相似文献
103.
AbstractA straightforward synthesis of acylating reagents such as Weinreb and MAP amides from aromatic, aliphatic carboxylic acids, and amino acids using PPh3/NBS combination is described. A chemo-selective modification of the carboxylic acid group into Weinreb amide in the presence of more reactive aldehydes and ketones is presented. All reactions were performed at ambient temperature under air using undried commercial grade solvent. Furthermore, the present methodology could be performed at a gram scale under inert-free reaction conditions. In addition, 7-azaindoline amide auxiliary (used for catalytic asymmetric aldol- and Mannich-type reactions), which behaves like Weinreb amide is also synthesized under similar reaction conditions. 相似文献
104.
105.
Dr. Binglin Sui Xinglei Liu Dr. Mengyuan Wang Prof. Kevin D. Belfield 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(30):10351-10354
A highly water‐soluble, fluorescence turn‐on sensor for Ca2+ is reported. The sensor affords high selectivity in sensing Ca2+ over other biologically important metal cations. The dissociation constant of the sensor in binding Ca2+ is 0.92 mm . Fluorescence microscopy experiments demonstrate that the sensor is cell‐impermeable and capable of detecting extracellular Ca2+. 相似文献
106.
《Angewandte Chemie (International ed. in English)》2017,56(40):12352-12355
Psilocybin is the psychotropic tryptamine‐derived natural product of Psilocybe carpophores, the so‐called “magic mushrooms”. Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes, namely i) PsiD, which represents a new class of fungal l ‐tryptophan decarboxylases, ii) PsiK, which catalyzes the phosphotransfer step, iii) the methyltransferase PsiM, catalyzing iterative N‐methyl transfer as the terminal biosynthetic step, and iv) PsiH, a monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step‐economic route from 4‐hydroxy‐l ‐tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production. 相似文献
107.
Dr. Li-Qiang Song Ying-Ying Zhang Dr. Jin-Yue Pu Dr. Man-Cheng Tang Dr. Chao Peng Prof. Dr. Gong-Li Tang 《Angewandte Chemie (International ed. in English)》2017,56(31):9116-9120
The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM-A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however, the follow-up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane-bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase covalently associated with FAD, subsequently performs an oxidative deamination extracellularly. These results not only fill in the missing steps of SFM-A biosynthesis, but also reveal that a FAD-binding oxidoreductase catalyzes an unexpected deamination reaction through an unconventional extracellular pathway in Streptmyces bacteria. 相似文献
108.
The steady-state composition of articular cartilage has previously been described as a balance between the metabolism of matrix molecules and the loss of these components from the tissue. Single compartment kinetic models have previously been developed to describe the relationship between these processes and overall (spatially-averaged) concentration of matrix molecules. Here, we develop a continuum model to describe the relationship between spatially-varying matrix concentrations and the processes of matrix formation, binding, degradation, and molecular transport within and from the cartilage tissue. At steady-state, the resultant concentration profile, and also spatially-averaged concentration, are predicted to depend on the balance between diffusivity and binding rate, diffusivity and formation rate, and various rate processes, some of which depend on tissue thickness. The predicted concentration profile, for certain parameter values, exhibits similarities to that known to exist for the proteoglycan matrix component, suggesting that transport factors may play an important role in causing the spatial variation in this component. Under other conditions, the predicted concentration profile may have a large portion of bound components and be relatively constant, consistent with the known distribution of collagen in cartilage. Thus, the continuum model may provide insight into the biophysical mechanism underlying matrix distribution within different regions of articular cartilage. 相似文献
109.
Xiaoyun Lu Jeff B. Smaill Ke Ding 《Angewandte Chemie (International ed. in English)》2020,59(33):13764-13776
Drugs that function through allosteric inhibition of kinase signaling represent a promising approach for the targeted discovery of therapeutics. The majority of developed allosteric kinase inhibitors are characterized as type III and IV inhibitors that show good kinome selectivity but generally lack the subtype selectivity of same kinase family. Recently allosteric inhibitors have been developed that bind outside the catalytic kinase domain with high selectivity for specific kinase subtypes. Allosteric inhibitors that bind to the pseudokinase domain of pseudokinase or the extracellular domain of receptor tyrosine kinases are reviewed. We also review recent developments in the field of allosteric kinase inhibitors including examples of proteolysis targeting chimeras, and highlight the unique binding modes for each type of inhibitors and address future opportunities in this area. 相似文献
110.
Philipp Leippe Johannes Broichhagen Katia Cailliau Alexandra Mougel Marion Morel Colette Dissous Dirk Trauner Jrme Vicogne 《Angewandte Chemie (International ed. in English)》2020,59(17):6720-6723
Receptor tyrosine kinases (RTKs) are key regulators of cellular functions in metazoans. In vertebrates, RTKs are mostly activated by polypeptides but are not naturally sensitive to amino acids or light. Taking inspiration from Venus kinase receptors (VKRs), an atypical family of RTKs found in nature, we have transformed the human insulin (hIR) and hepatocyte growth factor receptor (hMET) into glutamate receptors by replacing their extracellular binding domains with the ligand‐binding domain of metabotropic glutamate receptor type 2 (mGluR2). We then imparted light sensitivity through covalent attachment of a synthetic glutamate‐based photoswitch via a self‐labelling SNAP tag. By employing a Xenopus laevis oocyte kinase activity assay, we demonstrate how these chimeric RTKs, termed light‐controlled human insulin receptor (LihIR) and light‐controlled human MET receptor (LihMET), can be used to exert optical control over the insulin or MET signaling pathways. Our results outline a potentially general strategy to convert RTKs into photoreceptors. 相似文献