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131.
Charmian Cher Marie-Helene Tremblay Jack R. Barber Shi Chung Ng Bin Zhang 《Applied biochemistry and biotechnology》2010,160(5):1450-1459
Protein phosphatase 5 (PP5) is an important protein phosphatase that is abundantly expressed in the central nervous system.
Recent studies showed that PP5 activity in the neocortex from patients with Alzheimer’s disease (AD) is decreased significantly,
suggesting that small molecule PP5 activator may have therapeutic potential for AD. We performed a biochemical screening for
PP5 activators with the microsource compound library. Chaulmoogric acid was identified to be an effective activator with EC50 value of 134.5 μM. Importantly, results from circular dichroism (CD) and limited proteolysis study showed that chaulmoogric
acid binds to a region of tetratricopeptide repeat (TPR) domain of PP5 resulting in complete loss of helical contents. These
results demonstrate a different mechanism of action from that of arachidonic acid, a known activator for PP5 dephosphorylation
activity. Synergistic activation of PP5 enzymatic activity was also observed with combined application of both compounds at
relatively low concentrations. Therefore, further structure activity relationship study of chaulmoogric acid may facilitate
the discovery of small molecules that can synergize with endogenous arachidonic acid for PP5 activation. 相似文献
132.
Tremblay AE Buist PH Hodgson D Dawson B Whittle E Shanklin J 《Magnetic resonance in chemistry : MRC》2006,44(6):629-632
1H-decoupled 19F NMR has been used to monitor the highly regioselective oxidation of a fluorine-tagged thia-fatty acid derivative by castor stearoyl-ACP delta9 desaturase. The major enzymatic product, after reductive work-up, was identified as 9-fluoro-1-nonanol. This compound could be easily distinguished from substrate and a 9-sulfoxy by-product on the basis of its 19F NMR chemical shift and spiking experiments using authentic standards. Structural assignment of the cleavage product was confirmed by GC-MS analysis of the enzymatic products. 相似文献
133.
Rakic B Clarke J Tremblay TL Taylor J Schreiber K Nelson KM Abrams SR Pezacki JP 《Chemistry & biology》2006,13(10):1051-1060
The hepatitis C virus (HCV) is a growing global health problem. Small molecules that interfere with host-viral interactions can serve as powerful tools for elucidating the molecular mechanisms of pathogenesis and defining new strategies for therapeutic development. Using a cell-based screen involving subgenomic HCV replicons, we identified the ability of 18 different abscisic acid (ABA) analogs, originally developed as plant growth regulators, to inhibit HCV replication. Three of these were further studied. One compound, here named origamicin, showed antiviral activity through the inhibition of host proteins involved in protein folding. Origamicin could therefore be an important tool for studying the maturation of both host and viral proteins. Herein we demonstrate an application for molecular scaffolds based on ABA for mammalian cell targets involved in protein folding. 相似文献
134.
M.G. Townsend J.R. Gosselin R.J. Tremblay L.G. Ripley D.W. Carson W.B. Muir 《Journal of Physics and Chemistry of Solids》1977,38(10):1153-1159
Magnetic susceptibilities and Mössbauer spectra recorded at temperatures between 4° and 300°K show that the low temperature form of Cu5FeS4, bornite, orders magnetically at 76±2°K. At a lower temperature 8°K a second magnetic phase transition occurs. The Mössbauer spectra suggest that there is significant partial disordering of cations and vacancies in tetrahedral holes of the face-centred cubic sulphur lattice. Thermoelectric power measurements indicate that bornite is a p-type semiconductor.For a three dimensional magnetic superexchange interaction between Fe(III) atoms a small super-transferred spin density would be required on intermediate Cu(I) atoms. 相似文献
135.
An axicon is used to focus a CO2-TEA laser pulse in a high pressure preionized mixture of He-N2. An amplified stimulated emission (ASE) effect at 337.1 nm (N2) is obtained. The dependence of inversion population on the electron density is shown. Also presented is the electron temperature as a function of the CO2 pulse intensity for different mixtures of He-N2. 相似文献
136.
137.
The present report describes the design and application of a dual sprayer system for high-throughput proteome analysis. This system comprises parallel solid-phase extraction cartridges used for preconcentration and desalting of proteolytic digests prior to nanoelectrospray mass spectrometry analyses. Tryptic peptides from in-gel digest of protein bands/spots are first adsorbed on styrene divinyl benzene membrane and subsequently eluted with a short plug of organic buffer prior to infusion to the mass spectrometer at a flow rate of typically 500 nL/min. Tryptic peptide eluting from the membrane are analyzed by the mass spectrometer by moving in turn each sprayer in front of the sampling orifice. Sequential injection, preconcentration and analyses of tryptic digests are typically achieved with a throughput of up to 3.5 min/sample and a detection limit of approximately 8-80 fmol per injection. Replicate injections of peptide mixtures indicated that reproducibility of peak areas ranged from relative standard deviations (RSD) of 1.1% to 4.5%. The application of this device is demonstrated for digests of gel-isolated proteins obtained from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of rat liver plasma membrane and from two-dimensional gel electrophoresis of total cell lysate extracts from human prostatic cancer cell. 相似文献
138.
Mélanie Tremblay 《Tetrahedron》2005,61(28):6824-6828
We report the enhancement of α-chymotrypsin activity in organic solvents using modified peptides bearing two crown ethers. The transesterification of N-acetyl-l-phenylalanine ethyl ester with 1-propanol was used as model reaction. Co-lyophilization of crown ether modified peptides with α-chymotrypsin prior to use resulted in an increase of enzyme catalytic activity in non-aqueous media. The efficiency of enzyme activation is dependent on the amino acid sequence of peptidic additives and on the positions of the amino acids bearing the crown ligand. 相似文献
139.
(-)-Menthone, an inexpensive chiral auxiliary, was used to prepare both enantiomers of alpha-amino acids, amino alcohols, or oxazolidinones. The sequence includes the S(N)2' displacement by a cuprate reagent and a Curtius rearrangement as key steps. 相似文献
140.
Recent measurements on thin metal films suggest a pulse model of resistance fluctuations in which scale similarity and power law spectra are only approximate. We show that such a pulse model is consistent with stationary Gaussian resistance fluctuations. This is to be contrasted with the phenomenological behavior, of fluctuations near phase transitions and in turbulent fluids where the fluctuations are non-Gaussian, but exhibit scale similarity of deep physical origin. We then critically examine other tests of the Gaussian behavior of the fluctuating voltageV(t) across a resistor. These include the relaxation of the conditional mean V(t)¦V(0)=V
0, and the spectrum ofV
2(t). We consider also the question of time reversal invariance. We further ask under what conditions 1/f noise can be measured through fluctuations of the Johnson noise power with no applied voltage. We emphasize that this possibility, suggested and observed by Voss and Clarke, requires thatV(t) contain a non-Gaussian component. 相似文献