排序方式: 共有48条查询结果,搜索用时 15 毫秒
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Ganesh K. Mothukuri Sangram S. Kale Carl L. Stenbratt Alessandro Zorzi Jonathan Vesin Julien Bortoli Chapalay Kaycie Deyle Gerardo Turcatti Laura Cendron Alessandro Angelini Christian Heinis 《Chemical science》2020,11(30):7858
Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three building blocks are coupled sequentially in efficient alkylation reactions that eliminate the need for product purification. We demonstrate the power of the approach by combinatorially reacting 15 bromoacetamide-activated tripeptides, 42 amines, and 6 bis-electrophile cyclization linkers to generate a 3780-compound library with minimal effort. Screening against thrombin yielded a potent and selective inhibitor (Ki = 4.2 ± 0.8 nM) that efficiently blocked blood coagulation in human plasma. Structure–activity relationship and X-ray crystallography analysis revealed that two of the three building blocks acted synergistically and underscored the importance of combinatorial screening in macrocycle development. The three-component library synthesis approach is general and offers a promising avenue to generate macrocycle ligands to other targets.Combination of three efficient chemical reactions allows for solution-phase synthesis of 3780 macrocycles and identification of potent thrombin inhibitor. 相似文献
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Ruelle V El Moualij B Zorzi W Ledent P Pauw ED 《Rapid communications in mass spectrometry : RCM》2004,18(18):2013-2019
In recent years, various mass spectrometry procedures have been developed for bacterial identification. The accuracy and speed with which data can be obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) could make this a powerful tool for environmental monitoring. However, minor variations in the sample preparation can influence the mass spectra significantly. Therefore, the first objectives of this study were the adjustment and the optimization of experimental parameters allowing a rapid identification of whole bacterial cells without laborious sample preparation. The tested experimental parameters were matrix, extraction solvent, salt content, deposition method, culture medium and incubation time. This standardized protocol was applied to identify reference and environmental bacterial strains of Escherichia coli, Salmonella and Acinetobacter. The environmental bacterial strains were isolated from sewage sludge using an original microextraction procedure based on repeated sonications and enzymatic treatments. The bacterial identification was realized by the observation of the respective genus-, species- and strain-specific biomarkers. This bacterial taxonomy could be completed within one hour, with minimal sample preparation, provided that sufficient bacteria had been collected prior to MALDI-TOF analysis. 相似文献
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Tancini F Yebeutchou RM Pirondini L De Zorzi R Geremia S Scherman OA Dalcanale E 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(48):14313-14321
The outstanding complexing properties of tetraphosphonate cavitands towards N‐methylpyridinium salts were exploited to realise a new class of linear and cyclic AABB supramolecular polymers through host–guest interactions. The effectiveness of the selected self‐association processes was tested by 1H NMR studies, whereas microcalorimetric analyses clarified the binding thermodynamics and revealed the possibility of tuning entropic contributions by acting on the flexibility of the guest linker. Although the formation of linear polymeric chains for a rigid system was demonstrated by X‐ray analysis, the presence of a concentration‐dependent ring–chain equilibrium was indicated by solution viscosity measurements in the case of a very flexible ditopic BB guest co‐monomer. 相似文献
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We describe the development of hybrid nanoparticles composed of cationized gelatin and the polyanions CS and DS for gene therapy in the ocular surface. The physicochemical properties of the nanoparticles that impact their bioperformance, such as average size and zeta potential, can be conveniently modulated by changing the ratio of polymers and the crosslinker. These systems associate plasmid DNA and are able to protect it from DNase I degradation. We corroborate that the introduction of CS or DS in the formulation decreases the in vitro toxicity of the nanoparticles to human corneal cells without compromising the transfection efficiency. These nanoparticles are potential candidates for the development of safer and more effective nanomedicines for ocular therapy. 相似文献
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Molar extinction coefficients of some carbohydrates viz. l-arabinose (C5H10O5), d-glucose (C6H12O6), d-mannose (C6H12O6), d-galactose (C6H12O6), d(-) fructose (C6H12O6) and maltose (C12H24O12) in aqueous solutions have been determined at 81, 356, 511, 662, 1173 and 1332 keV by gamma ray transmission method in a
narrow beam good geometry set-up. These coefficients have been found to depend upon the photon energy following a 4-parameter
polynomial. These extinction coefficients for different sugars having the same molecular formula have same values varying
within experimental uncertainty. Within concentration ranges studied, Beer-Lambert law is obeyed very well. 相似文献
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Stefania?Gaudino Chiara?Galas Maria?Belli Sabrina?Barbizzi Paolo?de?Zorzi Radojko?Ja?imovi? Zvonka?Jeran Alessandra?Pati Umberto?SansoneEmail author 《Accreditation and quality assurance》2007,12(2):84-93
The measurement of trace-element concentration in soil, sediment and waste, is generally a combination of a digestion procedure
for dissolution of elements and a subsequent measurement of the dissolved elements. “Partial” and “total” digestion methods
can be used in environmental monitoring activities. To compare measurement results obtained by different methods, it is crucial
to determine and to maintain control of the bias of the results obtained by these methods. In this paper, ICP-MS results obtained
after matrix digestion with modified aqua regia (HCl+HNO3+H2O2) method and two “total” digestion methods (microwave aqua regia+HF and HNO3+HF) are compared with those obtained by instrumental neutron activation analysis, a non-destructive analytical method for
the determination of the total mass concentrations of inorganic components in environmental matrices. The comparison was carried
out on eight agricultural soil samples collected in one test area and measured by k0-INAA and ICP-MS to determine As, Co, Cr, Sb and Zn mass concentration. The bias of results for As, Cd, Co, Cr, Cu, Ni, Pb,
Sb and Zn of the three digestion methods were assessed using selected measurement standards. This paper highlights that the
digestion procedure is an integral part of the measurement and can affect the measurement result in environmental analysis. 相似文献
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De Zorzi R Dubessy B Mulatier JC Geremia S Randaccio L Dutasta JP 《The Journal of organic chemistry》2007,72(12):4528-4531
Four tetraphosphorylated TiiiiPO cavitands 1 encapsulate the pyridinium heads of a tetrakis(N-methylpyridinium)porphyrin iodide to form a 4:1:4 (host)4/guest4+/4I- complex. The single-crystal X-ray diffraction analysis shows the arrangement of the four cavities bound to the CH3N+ groups of the porphyrin moiety and the four iodide anions nested between the phenethyl substituents of the hosts. 1H NMR investigations show that the structure is preserved in chloroform solution and underscore the effect of the counteranions. 相似文献