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31.
Kuberan B Beeler DL Lawrence R Lech M Rosenberg RD 《Journal of the American Chemical Society》2003,125(41):12424-12425
We have engineered a two-step enzymatic synthesis of Mitrin which is a more potent and homogeneous anticoagulant than the current animal-derived heparin. This engineered heparin may have advantages of being free from animal-derived pathogens and may also have reduced side effects such as heparin induced thrombocytopenia. This approach can also be extended to tailor heparin-based drugs with improved therapeutic characteristics to treat other disorders or infections in which heparin-like molecules play a major role. 相似文献
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33.
Zbigniew Kisiel Lech Pszczó?kowski Steven B. Charnley 《Journal of Molecular Spectroscopy》2007,241(2):220-229
The rotational spectrum of pyruvic acid has been investigated for the first time in the millimeter-wave region, at 160-314 GHz, and also in supersonic expansion, at 10-17.4 GHz. The analysis of the broadband spectra recorded in this work was carried out with the newly developed AABS software package for Assignment and Analysis of Broadband Spectra, and precise spectroscopic constants are reported for the ground state, the first excited state of the low-frequency skeletal torsional mode ν24, and the first excited state of the methyl torsional mode ν23. Limited results have also been obtained for several higher excited states. The dataset for the ground state currently exceeds 1500 lines and for both the A and E internal rotor sublevels spans the complete range of values of Ka at the mid values of J for the measured transitions. The results were analysed with three freely available computer programs employing different strategies for dealing with internal rotation and a comparative discussion of their merits is made. 相似文献
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35.
Leszek Pazderski Tomasz Pawlak Jerzy Sitkowski Lech Kozerski Edward Szłyk 《Magnetic resonance in chemistry : MRC》2010,48(6):450-457
1H, 13C and 15N NMR studies of iron(II), ruthenium(II) and osmium(II) tris‐chelated cationic complexes with 2,2′‐bipyridine and 1,10‐phenanthroline of the general formula [M(LL)3]2+ (M = Fe, Ru, Os; LL = bpy, phen) were performed. Inconsistent literature 1H signal assignments were corrected. Significant shielding of nitrogen‐adjacent protons [H(6) in bpy, H(2) in phen] and metal‐bonded nitrogens was observed, being enhanced in the series Ru(II) → Os(II) → Fe(II) for 1H, Fe(II) → Ru(II) → Os(II) for 15N and bpy → phen for both nuclei. The carbons are deshielded, the effect increasing in the order Ru(II) → Os(II) → Fe(II). Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
36.
Lech Maligranda Volodymyr V. Mykhaylyuk 《Journal of Mathematical Analysis and Applications》2011,375(2):401-411
A negative solution of Problem 188 posed by Max Eidelheit in the Scottish Book concerning superpositions of separately absolutely continuous functions is presented. We discuss here this and some related problems which have also negative solutions. Finally, we give an explanation of such negative answers from the “embeddings of Banach spaces” point of view. 相似文献
37.
Karolina Hyz Robert Kawȩcki Elżbieta Bednarek Wojciech Bocian Jerzy Sitkowski Lech Kozerski 《Magnetic resonance in chemistry : MRC》2010,48(8):575-584
Topotecan (TPT) is in clinical use as an antitumor agent, hycamtin?. Because of this, it requires both biologically and chemically useful information to be available. TPT acts by binding to the covalent complex formed by nicked DNA and topoisomerase I. This has a poisonous effect since inserted into the single‐strand nick and TPT inhibits its religation. We used NMR to trace TPT dynamics, tautomerism and solvolysis products in various solvents and conditions. Chemical stability was assessed in methanol and DMSO as compared to water, and the regioselectivity of the N‐ and O‐methylation was studied using various alkylating agents. The reaction products of quaternization of the nitrogen atom and methylation of the oxygen atom were characterized by means of ESI MS, 1H/13C‐HMBC and ‐HSQCAD NMR. We have focused on the NMR characterization of TPT with an anticipation that its aggregation, tumbling properties and the intramolecular dipolar interactions will be a common feature for other compounds described in this article. These features can also be useful in tracing the interactions of this class of topoisomerase I (TopoI) poisons with DNA. Moreover, the results explained shed light on the recently disclosed problem of lack of stability of TPT in the heart tissue homogenate samples using the analytical assays developed for this class of compounds carried out in the presence of methanol. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
38.
Thermogravimetric analysis was applied to the characterization of the porosity of silica gels. Results from thermogravimetric method are compared with those obtained from the nitrogen method. The consistency of the parameters characterizing the porous structure of silica gels derived from the data of various methods is satisfactory. 相似文献
39.
Dr. Lech‐Gustav Milroy Dr. Maria Bartel Dr. Morkos A. Henen Dr. Seppe Leysen Joris M. C. Adriaans Prof. Dr. Luc Brunsveld Dr. Isabelle Landrieu Dr. Christian Ottmann 《Angewandte Chemie (International ed. in English)》2015,54(52):15720-15724
The discovery of novel protein–protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein–stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X‐ray crystallographic data from both stabilizer and inhibitor co‐crystal complexes of the adapter protein 14‐3‐3 to characterize, down to the atomic scale, inhibitors of the 14‐3‐3/Tau PPI, a potential drug target to treat Alzheimer’s disease. The most potent compound notably inhibited the binding of phosphorylated full‐length Tau to 14‐3‐3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer–protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14‐3‐3 and other PPIs. 相似文献
40.
Xianwen Lou Bas F. M. de Waal Lech‐Gustav Milroy Joost L. J. van Dongen 《Journal of mass spectrometry : JMS》2015,50(5):766-770
In matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI TOF MS), analyte signals can be substantially suppressed by other compounds in the sample. In this technical note, we describe a modified thin‐layer sample preparation method that significantly reduces the analyte suppression effect (ASE). In our method, analytes are deposited on top of the surface of matrix preloaded on the MALDI plate. To prevent embedding of analyte into the matrix crystals, the sample solution were prepared without matrix and efforts were taken not to re‐dissolve the preloaded matrix. The results with model mixtures of peptides, synthetic polymers and lipids show that detection of analyte ions, which were completely suppressed using the conventional dried‐droplet method, could be effectively recovered by using our method. Our findings suggest that the incorporation of analytes in the matrix crystals has an important contributory effect on ASE. By reducing ASE, our method should be useful for the direct MALDI MS analysis of multicomponent mixtures. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献