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271.
McGouran JF Kramer HB Mackeen MM di Gleria K Altun M Kessler BM 《Organic & biomolecular chemistry》2012,10(17):3379-3383
Novel ubiquitin-based active site probes including a fluorescent tag have been developed and evaluated. A new, functionalizable electrophilic trap is utilized allowing for late stage diversification of the probe. Attachment of fluorescent dyes allowed direct detection of endogenous deubiquitinating enzyme (DUB) activities in cell extracts by in-gel fluorescence imaging. 相似文献
272.
Yuan Y Arnatt CK Li G Haney KM Ding D Jacob JC Selley DE Zhang Y 《Organic & biomolecular chemistry》2012,10(13):2633-2646
The bivalent ligand approach has been utilized not only to study the underlying mechanism of G protein-coupled receptors dimerization and/or oligomerization, but also to enhance ligand affinity and/or selectivity for potential treatment of a variety of diseases by targeting this process. Substance abuse and addiction have made both the prevention and the treatment of human immunodeficiency virus (HIV) infection more difficult to tackle. Morphine, a mu opioid receptor (MOR) agonist, can accelerate HIV infection through up-regulating the expression of the chemokine receptor CCR5, a well-known co-receptor for HIV invasion to the host cells and this has been extensively studied. Meanwhile, two research groups have described the putative MOR-CCR5 heterodimers in their independent studies. The purpose of this paper is to report the design and synthesis of a bivalent ligand to explore the biological and pharmacological process of the putative MOR-CCR5 dimerization phenomenon. The developed bivalent ligand thus contains two distinct pharmacophores linked through a spacer; ideally one of which will interact with the MOR and the other with the CCR5. Naltrexone and Maraviroc were selected as the pharmacophores to generate such a bivalent probe. The overall reaction route to prepare this bivalent ligand was convergent and efficient, and involved sixteen steps with moderate to good yields. The preliminary biological characterization showed that the bivalent compound 1 retained the pharmacological characteristics of both pharmacophores towards the MOR and the CCR5 respectively with relatively lower binding affinity, which tentatively validated our original molecular design. 相似文献
273.
Chen LH Xu ST Li XY Tian G Li Y Rooke JC Zhu GS Qiu SL Wei YX Yang XY Liu ZM Su BL 《Journal of colloid and interface science》2012,377(1):368-374
Hierarchical porous architecture with interconnected trimodal micro-meso-macroporous systems constructed from uniform zeolite Zr-doped silicalite-1 nanocrystals has been prepared. The synthesis has been made by using glycerin as a reaction medium via a quasi-solid-state crystallization of hierarchically meso-macroporous zirconosilicate precursor under the effect of the structure directing agent TPAOH. The presence of glycerin is crucial in the synthesis systems to maintain the porous hierarchy. The pores inter-connectivity, Zr location in the framework, the acidity and the catalytic activity have been studied by laser-hyperpolarized (129)Xe NMR spectroscopy, UV-visible spectroscopy, temperature-programmed desorption of ammonia and the catalytic isopropylbenzene cracking probe reaction, respectively. The products possess well-defined macrochannels interconnected with mesopores located in the macropore walls, which in turn have been constructed from microporous MFI-type zeolite units. (129)Xe NMR study indicated that the hierarchically micro-, meso-, macro-pore systems are homogeneously distributed throughout the final materials and well interconnected, which is important for molecular diffusion. The TPD-NH(3) investigation revealed that the hierarchically micro-meso-macroporous materials constructed from zeolite Zr-Silicalite-1 nanocrystals present strong acidity. 相似文献
274.
The surface properties of aluminosilicates (perlites and zeolites)—potential fillers in abrasive articles—have been examined by inverse gas chromatography. The dispersive component of the surface free energy ( $ \gamma_{\text{S}}^{\text{D}} $ ) and K A and K D describing the acidity and basicity, respectively, of the fillers were used to express the surface activity of examined materials. The Flory–Huggins parameter, $ \chi_{23}^{'} , $ characterized the interactions between polymer and filler, i.e., interactions between phenolic resin and filler. Zeolites were found to be materials with an active surface layer and relatively high ability to participate in filler–resin interactions. Therefore, they might be considered as potential “replacement material” for standard fillers. The IGC-derived values mentioned above provided useful information about the behavior of fillers during the manufacture and use of abrasive articles. 相似文献
275.
Pozsgay V Kubler-Kielb J Coxon B Santacroce P Robbins JB Schneerson R 《The Journal of organic chemistry》2012,77(14):5922-5941
Escherichia coli O148 is a nonencapsulated enterotoxigenic (ETEC) Gram negative bacterium that can cause diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome in humans. The surface-exposed O-specific polysaccharide (O-SP) of the lipopolysaccharide of this bacterium is considered both a virulence factor and a protective antigen. It is built up of the linear tetrasaccharide repeating unit [3)-α-L-Rhap-(1→2)-α-D-Glcp-(1→3)-α-D-GlcNAcp-(1→3)-α-L-Rhap-(1→] differing from that of the O-SP of Shigella dysenteriae type 1 (SD) only in that the latter contains a D-Galp residue in place of the glucose moiety of the former. The close similarity of the O-SPs of these bacteria indicated a possible cross-reactivity. To answer this question we synthesized several oligosaccharide fragments of E. coli O148 O-SP, up to a dodecasaccharide, as well as their bovine serum albumin or recombinant diphtheria toxin conjugates. Immunization of mice with these conjugates induced anti-O-SP-specific serum IgG antibody responses. The antisera reacted equally well with the LPSs of both bacteria, indicating cross-reactivity between the SD and E. coli O148 O-SPs that was further supported by Western-blot and dot-blot analyses, as well as by inhibition of binding between the antisera and the O-SPs of both bacteria. 相似文献
276.
Studies are constantly being conducted on the elaboration of efficient methods to confirm the compatibility of active pharmaceutical ingredients (APIs) and excipients, since medicinal products, apart from their APIs, also contain numerous excipients that not only have important functions in pharmaceutical preparations but can also initiate or participate in interactions with drug substances, which eventually lead to a decline in drug quality. With this in mind, research was undertaken to evaluate two of the most often applied pattern recognition methods, hierarchical cluster analysis (HCA) and principal component analysis (PCA), as supporting techniques in the identification of potential physicochemical interactions that may occur during the preformulation of solid dosage forms. The investigation performed with the use of baclofen and selected excipients has shown that with thermogravimetric analysis, HCA and PCA fulfill their role as supporting techniques in the interpretation of the data obtained. Based on these methods, it is possible to detect incompatibilities between baclofen and excipients, and the data obtained concur strongly with the results of differential scanning calorimetry and IR spectrometry analyses. 相似文献
277.
Metallo-β-lactamases (mβls) cause bacterial resistance toward a broad spectrum of β-lactam antibiotics by catalyzing the hydrolytic cleavage of the four-membered β-lactam ring, thus inactivating the drug. Minutiae of the mechanism of these enzymes are still not well understood, and reports about binding studies of the substrates to the enzymes as well as to synthetic model systems are rare. Here we report a new pyrazolate-based bioinspired dizinc complex (1) reminiscent of the active site of binuclear mβls. Since 1 does not mediate hydrolytic degradation of β-lactams, the binding of a series of common β-lactam antibiotics (benzylpenicillin, cephalotin, 6-aminopenicillanic acid, ampicillin) as well as the inhibitor sulbactam and the simplest β-lactam, 2-azetidinone, to the dizinc core of 1 could now be studied in detail by NMR and IR spectroscopy as well as mass spectrometry. X-ray crystallographic information was obtained for 1 and its complexes with 2-azetidinone (2) and sulbactam (3); the latter represents the first structurally characterized dizinc complex with a bound β-lactam drug. While 2-azetidinone was found deprotonated and bridging in the clamp of the two zinc ions in 2, in 3 and all other cases the substrates preferentially bind via their carboxylate group within the bimetallic pocket. The relevance of this binding mode for mβls and consequences for the design of functional model systems are discussed. 相似文献
278.
Joanna Kobyłecka Bogdan Ptaszyński Anna Zwolinńska 《Monatshefte für Chemie / Chemical Monthly》2000,131(1):1-11
Summary. Sparingly water soluble complexes of lead(II), cadmium(II), and zinc(II) with N-phosphonomethylglycine (glyphosate, NPMG) of the general formulae C3H6O5NPPb, C3H6O5NPCdċ2H2O, and C3H6O5NPZn were synthesized. The complexes were also precipited from a dilute Roundup solution, and their solubility in water was
determined. Thermal, diffractometric, and IR spectrophotometric analyses were carried out. It was found that the metal is
bonded to glyphosate through the oxygen atoms of the carboxylic and phosphonate groups; metal-nitrogen binding is absent in
the above compounds. Studying the complexing behaviour in solution by UV spectrophotometry pointed out that a complex of the
composition Pb(II) : NPMG=1:1 with an absorption band at 232 nm is formed. Its stability constant as determined by Job’s method is logK=5.9±0.1. Using potentiometric techniques, the dissociation constant of N-phosphonomethylglycine and the stability constants
of its complexes with cadmium (II) and zinc (II) were determined.
Received June 30, 1999/Accepted July 21, 1999. 相似文献
279.
Joanna Józefowska Marek Mika Rafał Różycki Grzegorz Waligóra Jan Weglarz 《Mathematical Methods of Operations Research》2000,52(3):489-499
In this paper a discrete-continuous project scheduling problem is considered. In this problem activities simultaneously require
discrete and continuous resources. The processing rate of each activity depends on the amount of the continuous resource allotted
to this activity at a time. All the resources are renewable ones. The activities are nonpreemtable and the objective is to
minimize the makespan. Discretization of this problem leading to a classical (i.e. discrete) project scheduling problem in
the multi-mode version is presented. A simulated annealing (SA) approach to solving this problem is described and tested computationally
in two versions: with and without finding an optimal continuous resource allocation for the final schedule. In the former
case a nonlinear solver is used for solving a corresponding convex programming problem. The results are compared with the
results obtained using SA for the discrete-continuous project scheduling problem where the nonlinear solver is used for exact
solving the continuous part in each iteration. The results of a computational experiment are analyzed and some conclusions
are included. 相似文献
280.
Joanna Brzeska Magda Morawska Aleksandra Heimowska Wanda Sikorska Wojciech Wałach Anna Hercog Marek Kowalczuk Maria Rutkowska 《Chemical Papers》2018,72(5):1249-1256
The surface morphology and thermal properties of polyurethanes can be correlated to their chemical composition. The hydrophilicity, surface morphology, and thermal properties of polyurethanes (differed in soft segments and in linear/cross-linked structure) were investigated. The influence of poly([R,S]-3-hydroxybutyrate) presence in soft segments and blending of polyurethane with polylactide on surface topography were also estimated. The linear polyurethanes (partially crystalline) had the granular surface, whereas the surface of cross-linked polyurethanes (almost amorphous) was smooth. Round aggregates of polylactide un-uniformly distributed in matrix of polyurethane were clearly visible. It was concluded that some modification of soft segment (by mixing of poly([R,S]-3-hydroxybutyrate) with different polydiols and polytriol) and blending of polyurethanes with small amount of polylactide influence on crystallinity and surface topography of obtained polyurethanes. 相似文献