Andrea M. Cook  Christian Wolf 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2016,128(8):2982-2986

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Prof. Dr. Steven H. Liang  Dr. Jinshan Michael Chen  Prof. Dr. Marc D. Normandin  Dr. Jeanne S. Chang  Dr. George C. Chang  Dr. Christine K. Taylor  Dr. Patrick Trapa  Dr. Mark S. Plummer  Dr. Kimberly S. Para  Dr. Edward L. Conn  Dr. Lori Lopresti‐Morrow  Dr. Lorraine F. Lanyon  Dr. James M. Cook  Dr. Karl E. G. Richter  Dr. Charlie E. Nolan  Dr. Joel B. Schachter  Dr. Fouad Janat  Dr. Ye Che  Dr. Veerabahu Shanmugasundaram  Dr. Bruce A. Lefker  Dr. Bradley E. Enerson  Prof. Dr. Elijahu Livni  Lu Wang  Dr. Nicolas J. Guehl  Dr. Debasis Patnaik  Florence F. Wagner  Prof. Dr. Roy Perlis  Dr. Edward B. Holson  Prof. Dr. Stephen J. Haggarty  Prof. Dr. Georges El Fakhri  Dr. Ravi G. Kurumbail  Prof. Dr. Neil Vasdev 《Angewandte Chemie (International ed. in English)》2016,55(33):9601-9605

Glycogen synthase kinase‐3 (GSK‐3) regulates multiple cellular processes in diabetes, oncology, and neurology. N‐(3‐(1H‐1,2,4‐triazol‐1‐yl)propyl)‐5‐(3‐chloro‐4‐methoxyphenyl)oxazole‐4‐carboxamide (PF‐04802367 or PF‐367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK‐3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF‐367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF‐367 is ideal for discovery of radiopharmaceuticals for GSK‐3 in the central nervous system. A ¹¹C‐isotopologue of PF‐367 was synthesized and preliminary PET imaging studies in non‐human primates confirmed that we have overcome the two major obstacles for imaging GSK‐3, namely, reasonable brain permeability and displaceable binding.  相似文献   

    

Brendan M. Monks  Erin R. Fruchey  Prof. Silas P. Cook 《Angewandte Chemie (International ed. in English)》2014,53(41):11065-11069

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Joseph P. Cook  Glenn W. Goodall  Olga V. Khutoryanskaya  Vitaliy V. Khutoryanskiy 《Macromolecular rapid communications》2012,33(4):332-336

It has been found that hydrogels may be formed by microwave irradiation of aqueous solutions containing appropriate combinations of polymers. This new method of hydrogel synthesis yields sterile hydrogels without the use of monomers, eliminating the need for the removal of unreacted species from the final product. Results for two particularly successful combinations, poly(vinyl alcohol) with either poly(acrylic acid) or poly(methylvinylether‐alt‐maleic anhydride), are presented. Irradiation using temperatures of 100–150 °C was found to yield hydrogels with large equilibrium swelling degrees of 500–1000 g g⁻¹. Material leached from both types of hydrogel shows little cytotoxicity towards HT29 cells.  相似文献   

    

Shannon L. Cook  Carolyn M. Zimmermann  David Singer  Maria Fedorova  Ralf Hoffmann  Glen P. Jackson 《Journal of mass spectrometry : JMS》2012,47(6):786-794

The fragmentation behavior of the 2+ and 3+ charge states of eleven different phosphorylated tau peptides was studied using collision‐induced dissociation (CID), electron transfer dissociation (ETD) and metastable atom‐activated dissociation (MAD). The synthetic peptides studied contain up to two known phosphorylation sites on serine or threonine residues, at least two basic residues, and between four and eight potential sites of phosphorylation. CID produced mainly b‐/y‐type ions with abundant neutral losses of the phosphorylation modification. ETD produced c‐/z‐type ions in highest abundance but also showed numerous y‐type ions at a frequency about 50% that of the z‐type ions. The major peaks observed in the ETD spectra correspond to the charge‐reduced product ions and small neutral losses from the charge‐reduced peaks. ETD of the 2+ charge state of each peptide generally produced fewer backbone cleavages than the 3+ charge state, consistent with previous reports. Regardless of charge state, MAD achieved more extensive backbone cleavage than CID or ETD, while retaining the modification(s) in most cases. In all but one case, unambiguous modification site determination was achieved with MAD. MAD produced 15–20% better sequence coverage than CID and ETD for both the 2+ and 3+ charge states and very different fragmentation products indicating that the mechanism of fragmentation in MAD is unique and complementary to CID and ETD. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

    

David J. Lowe  Andrew V. Chapman  Stuart Cook  James J. C. Busfield 《Journal of Polymer Science.Polymer Physics》2011,49(22):1621-1627

Small strain Young's moduli of natural rubber (NR)/organoclay nanocomposites were estimated using the Guth–Gold, Halpin–Tsai (HT), and Krieger–Dougherty (KD) models, and compared with experimental measurements of NR vulcanizates containing organo‐montmorillonite (OM) or organo‐sepiolite (OS). To account for the effect on modulus of the NR matrix of the vulcanization‐active modifier in the organoclay, a matrix modulus correction (MMC) term was derived from the vulcanization parameters of the nanocomposites. The KD model gave a better empirical fit with the experimental data than the Guth–Gold model, with both giving good agreement with particle shape factors estimated from transmission electron microscope (TEM) images. The HT model gave the best fit with experiment for both types of nanocomposite, and use of the MMC term meant that the empirical shape factor was sufficiently close to that estimated from TEM images that the model could potentially be used to accurately predict the Young's moduli of NR/OM and NR/OS nanocomposites. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1621–1627, 2011  相似文献   

    

Venkatesh Vasudevan  Robert D. Cook  Ronald K. Hanson  Craig T. Bowman  David M. Golden 《国际化学动力学杂志》2008,40(8):488-495

The reaction between methyl and hydroxyl radicals has been studied in reflected shock wave experiments using narrow‐linewidth OH laser absorption. OH radicals were generated by the rapid thermal decomposition of tert‐butyl hydroperoxide. Two different species were used as CH₃ radical precursors, azomethane and methyl iodide. The overall rate coefficient of the CH₃ + OH reaction was determined in the temperature range 1081–1426 K under conditions of chemical isolation. The experimental data are in good agreement with a recent theoretical study of the reaction. The decomposition of methanol to methyl and OH radicals was also investigated behind reflected shock waves. The current measurements are in good agreement with a recent experimental study and a master equation simulation. © 2008 Wiley Periodicals, Inc. 40: 488–495, 2008  相似文献   

    

Lim HK  Chen J  Cook K  Sensenhauser C  Silva J  Evans DC 《Rapid communications in mass spectrometry : RCM》2008,22(8):1295-1311

A need still exists for a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method that can detect broad classes of glutathione (GSH) conjugates and provide characterization of their structures. We now describe the development of a method that multiplexes high-resolution accurate mass analysis with isotope pattern triggered data-dependent product ion scans, for simultaneous detection and structural elucidation of GSH conjugates within a single analysis using a LTQ/Orbitrap. This method was initially developed to detect GSH conjugates generated from incubating 10 microM test compound with pooled human liver microsomes fortified with NADPH-regenerating system and a 2:1 ratio of 5 mM glutathione and [(13)C(2) (15)N-Gly]glutathione. The GSH conjugates were detected by isotope search of mass defect filtered and control subtracted full scan accurate MS data using MetWorks software. This was followed by elucidation of reactive intermediate structures using chemical formulae for both protonated molecules and their product ions from accurate masses in a single analysis. The mass accuracies measured for the precursor and product ions by the Orbitrap were <2 ppm in external mass calibration mode. Successful detection and characterization of GSH conjugates of acetaminophen, tienilic acid, clozapine, ticlopidine and mifepristone validated this method. In each case, the detected GSH conjugates were within the top five hits by isotope search. This method also has a broader detection capability since it is independent of the collision-induced dissociation behavior of the GSH conjugates. Furthermore, this method is amenable to a broad class of reactive intermediate trapping agents as exemplified by the simultaneous detection and structural elucidation of the cyano-N-methylene iminium ion conjugates of verapamil and its O-desmethyl metabolites, which we report for the first time. In addition to the chemically tagged reactive intermediates, this method also provides information on stable metabolites from the full scan accurate MS data.  相似文献   

Back Cover: Remarkably High Reactivity of Pd(OAc)2/Pyridine Catalysts: Nondirected C?H Oxygenation of Arenes (Angew. Chem. Int. Ed. 40/2011)     

Dr. Marion H. Emmert  Amanda K. Cook  Yushu J. Xie  Prof. Melanie S. Sanford 《Angewandte Chemie (International ed. in English)》2011,50(40):9508-9508

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Cook G  Timms PL  Göltner-Spickermann C 《Angewandte Chemie (International ed. in English)》2003,42(5):557-559

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