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991.
Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation 下载免费PDF全文
Dr. Pablo G. Jambrina Dr. Nora Rauch Dr. Ruth Pilkington Dr. Katja Rybakova Dr. Lan K. Nguyen Prof. Boris N. Kholodenko Dr. Nicolae‐Viorel Buchete Prof. Walter Kolch Dr. Edina Rosta 《Angewandte Chemie (International ed. in English)》2016,55(3):983-986
RAF kinases are key players in the MAPK signaling pathway and are important targets for personalized cancer therapy. RAF dimerization is part of the physiological activation mechanism, together with phosphorylation, and is known to convey resistance to RAF inhibitors. Herein, molecular dynamics simulations are used to show that phosphorylation of a key N‐terminal acidic (NtA) motif facilitates RAF dimerization by introducing several interprotomer salt bridges between the αC‐helix and charged residues upstream of the NtA motif. Additionally, we show that the R‐spine of RAF interacts with a conserved Trp residue in the vicinity of the NtA motif, connecting the active sites of two protomers and thereby modulating the cooperative interactions in the RAF dimer. Our findings provide a first structure‐based mechanism for the auto‐transactivation of RAF and could be generally applicable to other kinases, opening new pathways for overcoming dimerization‐related drug resistance. 相似文献
992.
Dr. Andrei S. Batsanov Prof. Dr. Javier A. Cabeza Dr. Marco G. Crestani Dr. Manuel R. Fructos Dr. Pablo García‐Álvarez Dr. Marie Gille Prof. Zhenyang Lin Prof. Dr. Todd B. Marder 《Angewandte Chemie (International ed. in English)》2016,55(15):4707-4710
Many transition‐metal complexes and some metal‐free compounds are able to bind carbon monoxide, a molecule which has the strongest chemical bond in nature. However, very few of them have been shown to induce the cleavage of its C?O bond and even fewer are those that are able to transform CO into organic reagents with potential in organic synthesis. This work shows that bis(pinacolato)diboron, B2pin2, reacts with ruthenium carbonyl to give metallic complexes containing borylmethylidyne (CBpin) and diborylethyne (pinBC≡CBpin) ligands and also metal‐free perborylated C1 and C2 products, such as C(Bpin)4 and C2(Bpin)6, respectively, which have great potential as building blocks for Suzuki–Miyaura cross‐coupling and other reactions. The use of 13CO‐enriched ruthenium carbonyl has demonstrated that the boron‐bound carbon atoms of all of these reaction products arise from CO ligands. 相似文献
993.
Peter B. Weber Raphael Hellwig Tobias Paintner Dr. Marie Lattelais Mateusz Paszkiewicz Pablo Casado Aguilar Peter S. Deimel Dr. Yuanyuan Guo Dr. Yi‐Qi Zhang Dr. Francesco Allegretti Dr. Anthoula C. Papageorgiou Dr. Joachim Reichert Dr. Svetlana Klyatskaya Prof. Dr. Mario Ruben Prof. Dr. Johannes V. Barth Dr. Marie‐Laure Bocquet Dr. Florian Klappenberger 《Angewandte Chemie (International ed. in English)》2016,55(19):5754-5759
Organocobalt complexes represent a versatile tool in organic synthesis as they are important intermediates in Pauson–Khand, Friedel–Crafts, and Nicholas reactions. Herein, a single‐molecule‐level investigation addressing the formation of an organocobalt complex at a solid–vacuum interface is reported. Deposition of 4,4′‐(ethyne‐1,2‐diyl)dibenzonitrile and Co atoms on the Ag(111) surface followed by annealing resulted in genuine complexes in which single Co atoms laterally coordinated to two carbonitrile groups undergo organometallic bonding with the internal alkyne moiety of adjacent molecules. Alternative complexation scenarios involving fragmentation of the precursor were ruled out by complementary X‐ray photoelectron spectroscopy. According to density functional theory analysis, the complexation with the alkyne moiety follows the Dewar–Chatt–Duncanson model for a two‐electron‐donor ligand where an alkyne‐to‐Co donation occurs together with a strong metal‐to‐alkyne back‐donation. 相似文献
994.
Andrea Gabriela Ochoa-Ruiz Guillermo Parra Diego López-Espinoza Pablo Astudillo Dmitry Galyamin Neus Sabaté Juan Pablo Esquivel Alba Adriana Vallejo-Cardona 《Electroanalysis》2023,35(4):e202200053
Electrochemical immunosensors comprise the merging of two different disciplines: molecular biology and electrochemistry. This review explains in depth the main parts of electrochemical immunosensors and how the enzyme-linked immunosorbent assay (ELISA) has been integrated into sophisticated “lab-on-a-chip” and “point-of-care” devices. It also reviews how nanotechnology has been a powerful tool for achieving lower detection limits, more signal amplification, and constructing label-free devices. It finally explores the new perspectives on electrochemical immunosensors to integrate them in novel paper microfluidic devices called EμPADs. Colleagues introducing themselves to the topic for the first time will find in this review a comprehensive revision of how the basics of the technology have given rise to the emerging topic of EμPADs. 相似文献
995.
Dr. Lucía Álvarez-Rodríguez Dr. Pablo Ríos Dr. Carlos J. Laglera-Gándara Andrea Jurado Dr. Francisco José Fernández-de-Córdova Prof. T. Brent Gunnoe Dr. Amor Rodríguez 《Angewandte Chemie (International ed. in English)》2023,62(34):e202306315
The synthesis and characterization of (tBuPBP)Ni(OAc) ( 5 ) by insertion of carbon dioxide into the Ni−C bond of (tBuPBP)NiMe ( 1 ) is presented. An unexpected CO2 cleavage process involving the formation of new B−O and Ni−CO bonds leads to the generation of a butterfly-structured tetra-nickel cluster (tBuPBOP)2Ni4(μ-CO)2 ( 6 ). Mechanistic investigation of this reaction indicates a reductive scission of CO2 by O-atom transfer to the boron atom via a cooperative nickel-boron mechanism. The CO2 activation reaction produces a three-coordinate (tBuP2BO)Ni-acyl intermediate ( A ) that leads to a (tBuP2BO)−NiI complex ( B ) via a likely radical pathway. The NiI species is trapped by treatment with the radical trap (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) to give (tBuP2BO)NiII(η2-TEMPO) ( 7 ). Additionally, 13C and 1H NMR spectroscopy analysis using 13C-enriched CO2 provides information about the species involved in the CO2 activation process. 相似文献
996.
Rosalba Sortino Marina Cunquero Gustavo Castro-Olvera Ricard Gelabert Miquel Moreno Fabio Riefolo Carlo Matera Noèlia Fernàndez-Castillo Luca Agnetta Michael Decker José M. Lluch Jordi Hernando Pablo Loza-Alvarez Pau Gorostiza 《Angewandte Chemie (International ed. in English)》2023,62(51):e202311181
To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton excitation, and has promoted two-photon photopharmacology and optogenetics. However, three-photon brain stimulation in vivo remains to be demonstrated. We report the regulation of neuronal activity in zebrafish larvae by three-photon excitation of a photoswitchable muscarinic agonist at 50 pM, a billion-fold lower concentration than used for uncaging, and with mid-infrared light of 1560 nm, the longest reported photoswitch wavelength. Robust, physiologically relevant photoresponses allow modulating brain activity in wild-type animals with spatiotemporal and pharmacological precision. Computational calculations predict that azobenzene-based ligands have high three-photon absorption cross-section and can be used directly with pulsed infrared light. The expansion of three-photon pharmacology will deeply impact basic neurobiology and neuromodulation phototherapies. 相似文献
997.
Prof. Dr. Pablo Wessig Dominik Badetko Lukas Wichterich Dr. Eric Sperlich Alexandra Kelling 《European journal of organic chemistry》2023,26(1):e202201234
The total syntheses of three arylnaphthalene lignans ( ANL s) were developed: Vitrofolal E ( 1 ), Noralashinol C ( 2 ), and Ternifoliuslignan E ( 3 ). These natural products have in common a missing substituent in 2-position of the naphthalene moiety ( 2H-ANL s). The key step of these syntheses is a regioselective intramolecular Photo-Dehydro-Diels-Alder (PDDA) reaction with (1,7)naphthalenophanes as primary products. A further improvement of the photochemical step was achieved by triplet sensitization with xanthone, allowing the use of more efficient UVA lamps. It should be noted that this work is a continuation of a previous publication about the total synthesis of lignans using the PDDA reaction.[1] 相似文献
998.
Blanco P Polyakov P Bou-Ali MM Wiegand S 《The journal of physical chemistry. B》2008,112(28):8340-8345
In the present work we studied the thermal diffusion behavior of n-decane in various alkanes by thermogravitational column (TC) technique and the thermal diffusion forced Rayleigh scattering (TDFRS) method. The investigated lighter alkanes compared to n-decane are n-pentane, n-hexane, n-heptane, n-octane, and the heavier ones are n-tetradecane, n-pentadecane, n-hexadecane, n-heptadecane, n-octadecane, and n-eicosane. The binary mixture n-decane/ n-pentane we investigated at several different concentrations; all other mixtures were only investigated at a mass fraction of 50%. Even for the volatile n-pentane/ n-decane mixture the deviations between the thermal diffusion coefficients determined by the different methods agreed within the error bars. Typically the agreement between the two methods was in the order of 5%. In comparison to recently published TC and TDFRS data we found deviations in the order of 30% up to 40%. We analyze and discuss the possible reasons for the discrepancies for the present and the past publications. 相似文献
999.
Patellamide A was efficiently synthesized from thiazole 2 via two complementary heterocyclization approaches to form the thiazole and oxazoline rings. 相似文献
1000.
Aptamers: molecular tools for analytical applications 总被引:3,自引:0,他引:3
Mairal T Ozalp VC Lozano Sánchez P Mir M Katakis I O'Sullivan CK 《Analytical and bioanalytical chemistry》2008,390(4):989-1007
Aptamers are artificial nucleic acid ligands, specifically generated against certain targets, such as amino acids, drugs,
proteins or other molecules. In nature they exist as a nucleic acid based genetic regulatory element called a riboswitch.
For generation of artificial ligands, they are isolated from combinatorial libraries of synthetic nucleic acid by exponential
enrichment, via an in vitro iterative process of adsorption, recovery and reamplification known as systematic evolution of
ligands by exponential enrichment (SELEX). Thanks to their unique characteristics and chemical structure, aptamers offer themselves
as ideal candidates for use in analytical devices and techniques. Recent progress in the aptamer selection and incorporation
of aptamers into molecular beacon structures will ensure the application of aptamers for functional and quantitative proteomics
and high-throughput screening for drug discovery, as well as in various analytical applications. The properties of aptamers
as well as recent developments in improved, time-efficient methods for their selection and stabilization are outlined. The
use of these powerful molecular tools for analysis and the advantages they offer over existing affinity biocomponents are
discussed. Finally the evolving use of aptamers in specific analytical applications such as chromatography, ELISA-type assays,
biosensors and affinity PCR as well as current avenues of research and future perspectives conclude this review. 相似文献