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541.
Vogt JA Schroer K Hölzer K Hunzinger C Klemm M Biefang-Arndt K Schillo S Cahill MA Schrattenholz A Matthies H Stegmann W 《Rapid communications in mass spectrometry : RCM》2003,17(12):1273-1282
An isotope dilution method for protein quantification is presented in the context of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS) and mass fingerprinting experiments, revealing an unappreciated high reproducibility and accuracy of relative peak intensity measurements. Labelled proteins were generated by growing cells in a medium containing (15)N-enriched amino acids, and were mixed with proteins of natural isotopic composition from control cells in ratios of approximately 0:1, 1:7, 1:2, 2:1, 7:1, and 1:0 (labelled/unlabelled). Mixtures were separated by two-dimensional gel electrophoresis and analysed by MALDI-TOFMS using typical experimental conditions. A linear relationship is demonstrated between the relative isotopologue abundances (RIA values) for particular peaks in the isotopic distribution of tryptic peptide fragments of the proteins, and the mole fractions of labelled proteins in the mixture. Analysis of RIA values (ARIA quantification) for peptides of six typical silver-stained protein spots for the various mixtures could reproduce the experimentally contrived ratios with approximate errors between 4% (2:1 mixture) and about 18% (1:7 mixture). A consideration of error and its propagation is discussed. ARIA does not require complete separation of the isotope patterns of labelled and unlabelled peptides, and is therefore advantageous in combination with all kinds of labelling experiments in biological systems, because it is compatible with minimal metabolic incorporation of labelling reagent. Simulations indicate that the minimum required (15)N enrichment of the total amino acid pool sufficient for ARIA is less than 4%. In an accompanying paper in this issue, we apply ARIA to proteins differentially labelled with isotope-coded alkylation reagents. 相似文献
542.
Gesa Schfer Jelena Mili Adeeb Eldahshan Frank Gtz Kerstin Zühlke Christian Schillinger Annika Kreuchwig Jonathan M. Elkins Kamal R. AbdulAzeez Andreas Oder Marie C. Moutty Nanako Masada Monika Beerbaum Brigitte Schlegel Sylvia Niquet Peter Schmieder Gerd Krause Jens Peter vonKries Dermot M. F. Cooper Stefan Knapp Jrg Rademann Walter Rosenthal Enno Klussmann 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2013,125(46):12409-12413
543.
Rita de Jesus Dr. Kerstin Hiesinger Prof. Dr. Manuel van Gemmeren 《Angewandte Chemie (International ed. in English)》2023,62(45):e202306659
C−H activation is an attractive methodology to increase molecular complexity without requiring substrate prefunctionalization. In contrast to well-established cross-coupling methods, C−H activation is less explored on large scales and its use in the production of pharmaceuticals faces substantial hurdles. However, the inherent advantages, such as shorter synthetic routes and simpler starting materials, motivate medicinal chemists and process chemists to overcome these challenges, and exploit C−H activation steps for the synthesis of pharmaceutically relevant compounds. In this review, we will cover examples of drugs/drug candidates where C−H activation has been implemented on a preparative synthetic scale (range between 355 mg and 130 kg). The optimization processes will be described, and each example will be examined in terms of its advantages and disadvantages, providing the reader with an in-depth understanding of the challenges and potential of C−H activation methodologies in the production of pharmaceuticals. 相似文献
544.
Dr. Monique J. Jacobs Dr. Guenter Schneider Dr. Kerstin G. Blank 《Angewandte Chemie (International ed. in English)》2016,55(8):2899-2902
Mechanophores, that is, molecules that show a defined response to force, are crucial building blocks of mechanoresponsive materials. The possibility of mechanically induced cycloreversion for a series of triazoles formed via strain‐promoted azide–alkyne cycloaddition reactions was investigated by density functional theory calculations, and these triazoles were compared to the 1,4‐ and 1,5‐regioisomers formed in the reaction of an azide with a terminal alkyne. We show that cycloreversion is in principal possible and that the pulling geometry is the most important parameter that determines the probability of cycloreversion. We further compared triazole stability to the mechanical stability of polymers that are frequently used as force transducers in mechanochemical experiments and identified DIBAC (azadibenzylcyclooctyne) as a promising mechanophore for future applications. 相似文献
545.
Manuel M. Bentlohner Laura‐Alice Jantke Thomas Henneberger Christina Fischer Kerstin Mayer Dr. Wilhelm Klein Prof. Dr. Thomas F. Fässler 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(39):13946-13952
The addition of Sn and Zn ions to [Ge9] clusters by reaction of [Ge9]4? with SnPh2Cl2, ZnCp*2 (Cp*=pentamethylcyclopentadienyl), or Zn2[HC(Ph2P=NPh)2]2 is reported. The resulting Sn‐ and Zn‐bridged clusters [(Ge9)M(Ge9)]q? (M=Sn, q=4; M=Zn, q=6) display various coordination modes. The M atoms that coordinate to the open square of a C4v‐symmetric [Ge9] cluster form strong covalent multicenter M?Ge bonds, in contrast to the M atoms coordinating to triangular cluster faces. Molecular orbital analyses show that the M atoms of the Ge9M fragments coordinate to a second [Ge9] cluster with similar orbitals but in different ways. The [Ge9Sn]2?unit donates two electrons to the triangular face of a second [Ge9]2? cluster with D3h symmetry, whereas [Ge9Zn]2?acts as an electron acceptor when interacting with the triangular face of a D3h‐symmetric [Ge9]4? unit. 相似文献
546.
Kerstin Mayer Lorenz J. Schiegerl Prof. Dr. Thomas F. Fässler 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(52):18794-18800
We report on the synthesis of new derivatives of silylated clusters of the type [Ge9(SiR3)3]? (R = SiMe3, Me = CH3; R = Ph, Ph = C6H5) as well as on their reactivity towards copper and zinc compounds. The silylated cluster compounds were synthesized by heterogeneous reactions starting from the Zintl phase K4Ge9. Reaction of K[Ge9{Si(SiMe3)3}3] with ZnCl2 leads to the already known dimeric compound [Zn(Ge9{Si(SiMe3)3}3)2] ( 1 ), whereas upon the reaction with [ZnCp*2] the coordination of [ZnCp*]+ to the cluster takes place (Cp*=1,2,3,4,5‐pentamethylcyclopentadienyl) under the formation of [ZnCp*(Ge9{Si(SiMe3)3}3)] ( 2 ). A similar reaction leads to [CuPiPr3(Ge9{Si(SiMe3)3}3)] ( 3 ) from [CuPiPr3Cl] (iPr=isopropyl). Further we investigated the novel silylated cluster units [Ge9(SiPh3)3]? ( 4 ) and [Ge9(SiPh3)2]? ( 5 ), which could be identified by mass spectroscopy. Bis‐ and tris‐silylated species can be synthesized by the respective stoichiometric reactions, and the products were characterized by ESI‐MS and NMR experiments. These clusters show rather different reactivity. The reaction of the tris‐silylated anion 4 with [CuPiPr3Cl] leads to [(CuPiPr3)3Ge9(SiPh3)2]+ as shown from NMR experiments and to [(CuPiPr3)4{Ge9(SiPh3)2}2] ( 6 ), which was characterized by single‐crystal X‐ray diffraction. Compound 6 shows a new type of coordination of the Cu atoms to the silylated Zintl clusters. 相似文献
547.
High content screening for G protein-coupled receptors using cell-based protein translocation assays
Grånäs C Lundholt BK Heydorn A Linde V Pedersen HC Krog-Jensen C Rosenkilde MM Pagliaro L 《Combinatorial chemistry & high throughput screening》2005,8(4):301-309
G protein-coupled receptors (GPCRs) have been one of the most productive classes of drug targets for several decades, and new technologies for GPCR-based discovery promise to keep this field active for years to come. While molecular screens for GPCR receptor agonist- and antagonist-based drugs will continue to be valuable discovery tools, the most exciting developments in the field involve cell-based assays for GPCR function. Some cell-based discovery strategies, such as the use of beta-arrestin as a surrogate marker for GPCR function, have already been reduced to practice, and have been used as valuable discovery tools for several years. The application of high content cell-based screening to GPCR discovery has opened up additional possibilities, such as direct tracking of GPCRs, G proteins and other signaling pathway components using intracellular translocation assays. These assays provide the capability to probe GPCR function at the cellular level with better resolution than has previously been possible, and offer practical strategies for more definitive selectivity evaluation and counter-screening in the early stages of drug discovery. The potential of cell-based translocation assays for GPCR discovery is described, and proof-of-concept data from a pilot screen with a CXCR4 assay are presented. This chemokine receptor is a highly relevant drug target which plays an important role in the pathogenesis of inflammatory disease and also has been shown to be a co-receptor for entry of HIV into cells as well as to play a role in metastasis of certain cancer cells. 相似文献
548.
549.
New amphiphiles with reactive tosylate groups and ionic sulfuric acid half esters based on the rod-like polysaccharide cellulose were designed via homogeneous tosylation followed by sulfation with the SO3-pyridine complex in N,N-dimethylacetamide. At appropriate degrees of functionalization the polymers are soluble both in water and dimethyl sulfoxide, and they are promising starting materials for self-organizing systems. 相似文献