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141.
A Multivalent Ligand for the Mannose‐6‐Phosphate Receptor for Endolysosomal Targeting of an Activity‐Based Probe
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Dr. Sascha Hoogendoorn Dr. Gijs H. M. van Puijvelde Prof. Dr. Johan Kuiper Prof. Dr. Gijs A. van der Marel Prof. Dr. Herman S. Overkleeft 《Angewandte Chemie (International ed. in English)》2014,53(41):10975-10978
The ubiquitously expressed mannose‐6‐phosphate receptors (MPRs) are a promising class of receptors for targeted compound delivery into the endolysosomal compartments of a variety of cell types. The development of a synthetic, multivalent, mannose‐6‐phosphate (M6P) glycopeptide‐based MPR ligand is described. The conjugation of this ligand to fluorescent DCG‐04, an activity‐based probe for cysteine cathepsins, enabled fluorescent readout of its receptor‐targeting properties. The resulting M6P‐cluster–BODIPY–DCG‐04 probe was shown to efficiently label cathepsins in cell lysates as well as in live cells. Furthermore, the introduction of the 6‐O‐phosphates leads to a completely altered uptake profile in COS and dendritic cells compared to a mannose‐containing ligand. Competition with mannose‐6‐phosphate abolished all uptake of the probe in COS cells, and we conclude that the mannose‐6‐phosphate cluster targets the MPR and ensures the targeted delivery of cargo bound to the cluster into the endolysosomal pathway. 相似文献
142.
Photoactivation of silver-exchanged zeolite A 总被引:1,自引:0,他引:1
143.
Johan Schubert 《International Journal of Approximate Reasoning》2012,53(2):176-189
We construct alternative frames of discernment from input belief functions. We assume that the core of each belief function is a subset of a so far unconstructed frame of discernment. The alternative frames are constructed as different cross products of unions of different cores. With the frames constructed the belief functions are combined for each alternative frame. The appropriateness of each frame is evaluated in two ways: (i) we measure the aggregated uncertainty (an entropy measure) of the combined belief functions for that frame to find if the belief functions are interacting in interesting ways, (ii) we measure the conflict in Dempster’s rule when combining the belief functions to make sure they do not exhibit too much internal conflict. A small frame typically yields a small aggregated uncertainty but a large conflict, and vice versa. The most appropriate frame of discernment is that which minimizes a probabilistic sum of the conflict and a normalized aggregated uncertainty of all combined belief functions for that frame of discernment. 相似文献
144.
Hubert Hřebabecký Milan Dejmek Martin Dračínský Michal Šála Pieter Leyssen Johan Neyts Martina Kaniaková Jan Krůšek Radim Nencka 《Tetrahedron》2012,68(4):1286-1298
Azanorbornylpurine derivatives were prepared by Mitsunobu reaction of appropriate hydroxyazanorbornane derivative with 6-chloropurine or construction of purine base at azanorbornylamines. The prepared target compounds were evaluated for antiviral activity and effect on neuronal and muscle nicotinic acetylcholine receptors. 相似文献
145.
Novel rapid liquid chromatography tandem masspectrometry method for vemurafenib and metabolites in human plasma,including metabolite concentrations at steady state
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Svante Vikingsson Malin Strömqvist Anna Svedberg Johan Hansson Veronica Höiom Henrik Gréen 《Biomedical chromatography : BMC》2016,30(8):1234-1239
A novel, rapid and sensitive liquid chromatography tandem–mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi‐quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi‐quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5–100 μg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
146.
147.
Erik Allard Rikard Åslund Tröger Björn Arvidsson Per Johan Ragnar Sjöberg 《Rapid communications in mass spectrometry : RCM》2010,24(4):429-435
Precision, reproducibility and lower limit of quantitation (LLOQ) are important characteristics of a quantitative method. We have investigated these properties for Ximelagatran (Xi), which has a high tendency to form doubly charged ions in electrospray ionization (ESI), by studying the percentage of doubly charged species formed when varying the formic acid (FA) concentration, analyte concentration, amount of organic modifier and flow rate. It was found that the percentage of [Xi + 2H]2+ can be controlled to be more than 90% or less than 10% by varying the amount of FA present, and that the change between these values is dramatic. Furthermore, the percentage of [Xi + 2H]2+ formed decreases with increased analyte concentration and increased flow rate. No apparent relationship with the amount of organic modifier was found. The results have the implication that, by carefully controlling the selected parameters, the LLOQ, precision and reproducibility can be improved. We have compared the fragmentation of the singly and doubly charged species and concluded that the [Xi + 2H]2+ ion is more inclined to undergo fragmentation than [Xi + H]+. As a consequence, unusual instrumental settings had to be used for the experiments. The fragmentation patterns are to a great extent similar, but the doubly charged species is more inclined to generate low‐mass product ions. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
148.
Back Cover: Supramolecular Wiring of Benzo‐1,3‐chalcogenazoles through Programmed Chalcogen Bonding Interactions (Chem. Eur. J. 16/2016)
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149.
Supramolecular Wiring of Benzo‐1,3‐chalcogenazoles through Programmed Chalcogen Bonding Interactions
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Dr. Adrian Kremer Dr. Andrea Fermi Nicolas Biot Prof. Johan Wouters Prof. Dr. Davide Bonifazi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(16):5665-5675
The high‐yielding synthesis of 2‐substituted benzo‐1,3‐tellurazoles and benzo‐1,3‐selenazoles through a dehydrative cyclization reaction has been reported, giving access to a large variety of benzo‐1,3‐chalcogenazoles. Exceptionally, these aromatic heterocycles proved to be very stable and thus very handy to form controlled solid‐state organizations in which wire‐like polymeric structures are formed through secondary N???Y bonding interactions (SBIs) engaging the chalcogen (Y=Se or Te) and nitrogen atoms. In particular, it has been shown that the recognition properties of the chalcogen centre at the solid state could be programmed by selectively barring one of its σ‐holes through a combination of electronic and steric effects exerted by the substituent at the 2‐position. As predicted by the electrostatic potential surfaces calculated by quantum chemical modelling, the pyridyl groups revealed to be the stronger chalcogen bonding acceptors, and thus the best ligand candidate for programming the molecular organization at the solid state. In contrast, the thiophenyl group is an unsuitable substituent for establishing SBIs in this molecular system as it gives rise to chalcogen–chalcogen repulsion. The weaker chalcogen donor properties of the Se analogues trigger the formation of feeble N???Se contacts, which are manifested in similar solid‐state polymers featuring longer nitrogen–chalcogen distances. 相似文献
150.