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1.
Orchestrating the Biosynthesis of an Unnatural Pyrrolysine Amino Acid for Its Direct Incorporation into Proteins Inside Living Cells 下载免费PDF全文
Michael Ehrlich Michael J. Gattner Bastien Viverge Johanna Bretzler Dr. David Eisen Michael Stadlmeier Dr. Milan Vrabel Prof. Dr. Thomas Carell 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(21):7701-7704
We here report the construction of an E. coli expression system able to manufacture an unnatural amino acid by artificial biosynthesis. This can be orchestrated with incorporation into protein by amber stop codon suppression inside a living cell. In our case an alkyne‐bearing pyrrolysine amino acid was biosynthesized and incorporated site‐specifically allowing orthogonal double protein labeling. 相似文献
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High‐Energy Long‐Lived Mixed Frenkel–Charge‐Transfer Excitons: From Double Stranded (AT)n to Natural DNA 下载免费PDF全文
Dr. Ignacio Vayá Dr. Johanna Brazard Dr. Miquel Huix‐Rotllant Dr. Arun K. Thazhathveetil Prof. Frederick D. Lewis Dr. Thomas Gustavsson Prof. Dr. Irene Burghardt Dr. Roberto Improta Dr. Dimitra Markovitsi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(14):4904-4914
The electronic excited states populated upon absorption of UV photons by DNA are extensively studied in relation to the UV‐induced damage to the genetic code. Here, we report a new unexpected relaxation pathway in adenine–thymine double‐stranded structures (AT)n. Fluorescence measurements on (AT)n hairpins (six and ten base pairs) and duplexes (20 and 2000 base pairs) reveal the existence of an emission band peaking at approximately 320 nm and decaying on the nanosecond time scale. Time‐dependent (TD)‐DFT calculations, performed for two base pairs and exploring various relaxation pathways, allow the assignment of this emission band to excited states resulting from mixing between Frenkel excitons and adenine‐to‐thymine charge‐transfer states. Emission from such high‐energy long‐lived mixed (HELM) states is in agreement with their fluorescence anisotropy (0.03), which is lower than that expected for π–π* states (≥0.1). An increase in the size of the system quenches π–π* fluorescence while enhancing HELM fluorescence. The latter process varies linearly with the hypochromism of the absorption spectra, both depending on the coupling between π–π* and charge‐transfer states. Subsequently, we identify the common features between the HELM states of (AT)n structures with those reported previously for alternating (GC)n: high emission energy, low fluorescence anisotropy, nanosecond lifetimes, and sensitivity to conformational disorder. These features are also detected for calf thymus DNA in which HELM states could evolve toward reactive π–π* states, giving rise to delayed fluorescence. 相似文献
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Annika Höhn Petra Hartmann Veronika Gebhart Johanna Sonntag Tilman Grune Tobias Jung 《Photochemistry and photobiology》2015,91(4):887-894
In this study, the athermal effects of water‐filtered infrared A (wIRA)‐irradiation (780–1400 nm) on human dermal fibroblasts were investigated. For this purpose, cells were exposed to wIRA‐irradiation (178 mW cm?2 for 1 h), while a sophisticated experimental setup prevented warming of the samples exceeding 0.1°C. The investigated parameters were the formation of reactive oxygen species (ROS), mitochondrial membrane potential and superoxide release, protein oxidation, proliferation rate, as well as intracellular Ca2+‐release in single cells, most of them quantified via fluorescence microscopy and fluorimetric techniques. The existence of actual athermal wIRA‐effects is still intensively discussed, since their detection requires a careful experimental setup and both efficient and powerful temperature regulation of the exposed samples. Here, we can definitively show that some of the supposed athermal wIRA‐effects may be rather artifacts, since wIRA did not reveal any impact on the above mentioned parameters—as long as the temperature of the exposed cells was carefully maintained. Though, we were able to identify an athermal DNA‐protective wIRA‐effect, since the induced DNA damage (quantified via 8‐Oxo‐G‐formation) was significantly decreased after a subsequent UVB‐exposure. These results suggest that many of the supposed athermal wIRA‐effects can be induced by pure warming of the samples, independent from any wIRA‐irradiation. 相似文献
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Veselin Nasufović Dr. Florian Küllmer Johanna Bößneck Dr. Hans-Martin Dahse Dr. Helmar Görls Dr. Peter Bellstedt Dr. Pierre Stallforth Prof. Dr. Hans-Dieter Arndt 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(45):11633-11642
The first total synthesis of the actin-stabilizing marine natural product geodiamolide H was achieved. Solid-phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring-closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F-actin target and property computation in silico, for a better understanding of structure-activity relationships (SAR). A non-natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design. 相似文献
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Dr. Samuel M. Meier M. Sc. Dominique Kreutz Dr. Lilli Winter M. Sc. Matthias H. M. Klose M. Sc. Klaudia Cseh M. Sc. Tamara Weiss Dr. Andrea Bileck M. Sc. Beatrix Alte Dr. Johanna C. Mader M. Sc. Samir Jana Dr. Annesha Chatterjee Dr. Arindam Bhattacharyya Michaela Hejl Dr. Michael A. Jakupec Priv.-Doz. Dr. Petra Heffeter Prof. Dr. Walter Berger Prof. Dr. Christian G. Hartinger Prof. Dr. Bernhard K. Keppler Prof. Dr. Gerhard Wiche Prof. Dr. Christopher Gerner 《Angewandte Chemie (International ed. in English)》2017,56(28):8267-8271
Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model. 相似文献
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Désirée L. Röhlen Johanna Pilas Michael J. Schöning Thorsten Selmer 《Applied biochemistry and biotechnology》2017,183(2):566-581
Three amperometric biosensors have been developed for the detection of l-malic acid, fumaric acid, and l -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for l-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM?1 (l-malate biosensor) and 0.4 μA mM?1 (fumarate biosensor). The l-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM?1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates. 相似文献
10.
Johanna Méndez Arias Anelize de Oliveira Moraes Luiz Felipe Amarante Modesto Aline Machado de Castro Nei Pereira Jr 《Applied biochemistry and biotechnology》2017,181(2):593-603
Poly(ethylene glycol) (PEG 4000) and bovine serum albumin (BSA) were investigated with the purpose of evaluating their influence on enzymatic hydrolysis of sugarcane bagasse. Effects of these supplements were assayed for different enzymatic cocktails (Trichoderma harzianum and Penicillium funiculosum) that acted on lignocellulosic material submitted to different pretreatment methods with varying solid (25 and 100 g/L) and protein (7.5 and 20 mg/g cellulose) loadings. The highest levels of glucose release were achieved using partially delignified cellulignin as substrate, along with the T. harzianum cocktail: increases of 14 and 18 % for 25 g/L solid loadings and of 33 and 43 % for 100 g/L solid loadings were reached for BSA and PEG supplementation, respectively. Addition of these supplements could maintain hydrolysis yield even for higher solid loadings, but for higher enzymatic cocktail protein loadings, increases in glucose release were not observed. Results indicate that synergism might occur among these additives and cellulase and xylanases. The use of these supplements, besides depending on factors such as pretreatment method of sugarcane bagasse, enzymatic cocktails composition, and solid and protein loadings, may not always lead to positive effects on the hydrolysis of lignocellulosic material, making it necessary further statistical studies, according to process conditions. 相似文献