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121.
Peptide-based reversible and irreversible cysteine proteases inhibitors are well reported in the literature. Many of these compounds have an electrophilic carbonyl group as a cysteine trap in the place of a scissile amide moiety of the natural substrate. As a common mechanism strategy, we have designed a probe library of a cysteine trap for rapid optimization of P1-P1' pockets of different cysteine proteases. The synthesis of this library using a straightforward methodology based on polymer-supported reagents and scavengers to avoid tedious purification steps has been achieved. For the selective monobromination of diazo ketones, preparation of a new supported reagent, piperidinoaminomethylpolystyrene hydrobromide, is also described. 相似文献
122.
Maréchal X Mordon S Devoisselle JM Bégu S Guery B Nevière R Buys B Dhelin G Lesage JC Mathieu D Chopin C 《Photochemistry and photobiology》1999,70(5):813-819
Measurement of gastrointestinal intramucosal pH (pHim) has been recognized as an important factor in the detection of hypoxia-induced dysfunctions. However, current pH measurement techniques are limited in terms of time and spatial resolutions. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). This study aimed to set up and validate a fluorescence imaging technique to measure in vivo the intramucosal pH (pHim) of the intestine. The intestine was inserted into an optical chamber placed under a microscope. Animals were injected intravenously with the pH-sensitive fluorescent dye BCECF. Fluorescence was visualized by illuminating the intestine alternately at 490 and 470 nm. The emitted fluorescence was directed to an intensified camera. The ratio of emitted fluorescence at excitation wavelengths of 490 and 470 nm was measured, corrected and converted to pHim by constructing a calibration curve. The pHim controls were performed with a pH microelectrode and were correlated with venous blood gas sampling. Results show that pHim is determined with an accuracy of +/- 0.07 pH units and a response time of 1 min. In conclusion pHim mapping of rat intestine can be obtained by fluorescence imaging using BCECF. This technology could be easily adapted for endoscopic pH measurements. 相似文献
123.
The open circuit dissolution of ionic metal oxides in mineral acids is modelled assuming that the rate is controlled by the transfer of metal ions in hydrolytic equilibrium with bulk metal ions, from the metal oxide surface to the Stern plane. The site-binding model of the double layer metal oxide/electrolyte solution is used to obtain the pH dependence of surface and Stern potentials. The nature of the active sites is discussed and their surface concentration is assumed to be proportional to suface charge σ0. Again, the site-binding model is used to detemine the pH dependence of σ0. It is thus shown that the rate order in cH+ is essentially defined by the potential dependence of the charge transfer process, for oxides with points of zero charge near neutrality that dissolve in mildly or strongly acidic solutions. The role of surface complexation is also discussed in terms of the site-binding model and the difficulties in interpreting dissolution experiments under constant external applied potential are discussed in terms of the complexity of the semiconductor oxide/electrolyte solution interfacial region in magnetite.An experimental study of the open circuit dissolution of magnetite in sulfuric acid is presented and interpreted according to the proposed model.The reductive dissolution of magnetite is modelled by extension of the Valverde-Wagner model of oxide dissolution. Experimental results are presented to demonstrate that the reductive dissolution rate of magnetite in ferrous containing solutions is controlled by the rate of electron transfer from adsorbed Fe(II) to Fe(III) surface states of magnetite. 相似文献
124.
We have studied gramicidin A, an environmentally sensitive polymorphic pentadecapeptide, fully 15N-labelled and dispersed in a highly deuterated phospholipid bilayer system. By submitting the sample to fast magic angle spinning, we were able to reduce the polypeptide amide hydrogen linewidths to 160 Hz, and hence to partially resolve them. By correlating these resonances with the 40 Hz wide dipolar coupled 15N in a 2D-CROPSY (cross-polarization spectroscopy) experiment, it was possible to observe the 20 partially overlapping 1H-15N signal pairs from the polypeptide backbone and sidechains. Both chemical shift distributions closely match those of the same peptide in SDS micelles, but only poorly match those of conformationally different gramicidin A in trifluoroethanol, dimethylsulfoxide, or methanol/chloroform mixture. Our results are indicative of the N-to-N right-handed beta6.3-helix conformation of gramicidin A and offer sufficient resolution to encourage development of experiments to measure orientational or distance restraints using through-space dipolar couplings. 相似文献
125.
Marie-Noelle Avettand-Fènoël N. David G. Reumont J. -M. Fiorani M. Vilasi P. Perrot 《Journal of Thermal Analysis and Calorimetry》2007,90(2):329-332
The Fe-Sn-Zn system is of interest because Sn is one element added to the Zn galvanizing bath to overcome the drawbacks due
to the presence of Si in semi-killed steels. This work has been undertaken with the aim to understand the tin effect on the
microstructure and the layers growth in batch galvanized coatings on low alloyed steels.
Various experimental techniques such as metallography, scanning electron microscopy (SEM) coupled with X-ray energy dispersive
spectroscopy (EDX) are used in order to characterize the microstructure and the properties of such coatings elaborated in
a zinc bath enriched with tin.
Solidification phenomena and layers growth mechanisms during galvanization are explained by means of the ternary phase diagram
Fe-Sn-Zn at 450°C. The Calphad method allows to obtain this phase diagram from the three optimized binary phase diagrams Fe-Sn,
Fe-Zn and Sn-Zn and some experimental data inside the ternary Fe-Sn-Zn system. 相似文献
126.
The CD. spectra of carotenoids in the 220-500 nm region may by inspection be classified as (a) essentially Conservative, (b) intermediate, or (c) essentially nonconservative. A conservative spectrum shows in that spectral region a sequence of 5-6 relatively sharp Cotton effects of alternating sign, the rotatory strengths of which roughly add to zero. In a non-conservative spectrum Δ? has the same sign over the whole region and its absolute value is in general somewhat smaller. In general, typical conservative spectra invert upon isomerization of the molecule from all-trans to mono-cis. Non-conservative spectra do not invert. The model of a chiral polyene of the length of the conjugated carotene chromophore reproduces well the main features of the conservative spectra. The theoretical predictions and the experimental data are shown to conform to the C2-rule [43] [44]. The particular nature of the longest-wavelength transition is interpreted. Based on a summary of the chiroptic data on about 50 naturally occurring compounds, the question is discussed of when conservative spectra arise and when not. 相似文献
127.
128.
Philippe Hennig Eric Raimbaud Christophe Thurieau Jean-Paul Volland André Michel Jean-Luc Fauchère 《Journal of computer-aided molecular design》1996,10(1):83-86
Summary The conformation in dimethylsulfoxide of the somatostatin derivative angiopeptin and of three disulfide-free analogs was estimated by two-dimensional nuclear magnetic resonance spectroscopy at room temperature. The resulting 3D molecular graphics were compared and shown to reflect the observed differences in the inhibition of restenosis after rat aorta balloon injury by these octapeptide inhibitors. Angiopeptin and its active analog 2 displayed a relatively rigid conformation of the cyclic hexapeptide backbone due to the presence of two well-defined hydrogen bonds, further stabilized by a third hydrogen bond outside the ring. No such constraints were detected for the two biologically inactive analogs, which, compared to 2, had a two-atom longer or shorter hexapeptide ring. The well-defined structure of compound 2 may serve as an improved pharmacophore for this new class of drugs. 相似文献
129.
Top S Vessières A Leclercq G Quivy J Tang J Vaissermann J Huché M Jaouen G 《Chemistry (Weinheim an der Bergstrasse, Germany)》2003,9(21):5223-5236
A series of ferrocene derivatives based upon the structure of the antiestrogenic drug tamoxifen or of its active metabolite hydroxytamoxifen has been prepared and named by analogy ferrocifens and hydroxyferrocifens. This series includes 1-[4-(O(CH(2))(n)NMe(2))phenyl]-1-phenyl-2-ferrocenyl-but-1-ene and 1-[4-(-O(CH(2))(n)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene, with n=2, 3, 5 and 8, and 1-[4-(-O(CH(2))(2)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenylethene. Most of these molecules have been synthesised by McMurry cross-coupling of the appropriate ketones, except for the ethene complexes, which were prepared by a four-step reaction sequence starting from the ferrocenylacetic acid. All these compounds were obtained as mixtures of Z and E isomers. The isomers were separated in the cases of the ferrocenyl derivatives of tamoxifen and hydroxytamoxifen (n=2). No isomerisation of the Z and E isomers occurred in DMSO after one day, while a 50:50 mixture of the isomers was obtained within one hour in chloroform. The X-ray structure of (E)-1-[4-(-O(CH(2))(2)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene has been determined. The relative binding affinity (RBA) values of the hydroxyferrocifens for the estrogen receptor alpha (ERalpha) was good to moderate, with values decreasing progressively with the length of the basic chain. The RBA values found for the estrogen receptor beta (ERbeta) are equal to or slightly less than those found for the alpha form. The lipophilicity of the hydroxyferrocifens are superior to the values found for estradiol and increase with lengthening of the chain. The antiproliferative effects of the four hydroxyferrocifens with n=2, 3, 5 and 8 were studied on four breast cancer cell lines (MCF7, MDA-MB231, RTx6 and TD5) possessing different levels of ERalpha. On MCF7 cells containing high levels of ERalpha, hydroxyferrocifens behave as antiestrogens. At a molarity of 1 microM the effect is close to that of hydroxytamoxifen (used for reference) when n=2 or 5, more marked when n=3, and weaker when n=8. Ferrocene alone has no effect. For the MDA-MB231 cells, classed as a hormone-independent breast cancer cell line, on the other hand, the hydroxyferrocifens show remarkable antiproliferative behaviour while the hydroxytamoxifen is completely inactive. Hydroxyferrocifens therefore show the unique property of being active both on hormone-dependent and on hormone-independent breast cancer cell lines. The molecular modelling study provides some clues for understanding of the antagonist effect of these molecules, while an additional cytotoxic effect due to the vectorised ferrocenyl unit is revealed in some occasions. 相似文献
130.
Y Masuo H Wang D Pélaprat Z Q Chi W Rostène 《Chemical & pharmaceutical bulletin》1992,40(9):2520-2524
We have recently demonstrated that [3H]ohmefentanyl, a non-peptidergic opioid ligand which was suggested to cross the blood brain barrier in contrast to other peptidergic opioid ligands, bound not only to mu opioid receptor sites but also to sigma sites. In order to examine whether [3H]ohmefentanyl can be used as a marker for mu sites, we investigated the effects of brain lesions on [3H]ohmefentanyl binding site densities, as compared with [3H][D-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]DAGO), a selective mu ligand. These binding site densities were measured by quantitative autoradiography in the rat striatum and substantia nigra, two brain structures known to contain a high density of mu receptors, following lesions of the nigro-striatal dopaminergic pathway and striatal intrinsic neurons. Following unilateral nigral lesion with 6-hydroxydopamine, [3H]ohmefentanyl binding site densities were decreased in the patches (-35%) and matrix (-20%) of the ipsilateral striatum and in the lesioned substantia nigra pars compacta (-49%). Unilateral striatal lesion with quinolinic acid induced 72%, 61% and 50% decreases in [3H]ohmefentanyl binding in the patches and matrix of the lesioned striatum and in the ipsilateral substantia nigra pars reticulata, respectively. Similar results were obtained in the binding of [3H]DAGO. Indeed, a significant linear correlation was observed between [3H]ohmefentanyl and [3H]DAGO binding site densities. Therefore, mu opioid receptors may be mainly located on intrinsic neurons in the striatum, dopaminergic cell bodies in the substantia nigra pars compacta and nerve terminals of striatal efferents in the substantia nigra pars reticulata.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献