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11.
Jo E Sanna MG Gonzalez-Cabrera PJ Thangada S Tigyi G Osborne DA Hla T Parrill AL Rosen H 《Chemistry & biology》2005,12(6):703-715
The essential role of the sphingosine 1-phosphate (S1P) receptor S1P(1) in regulating lymphocyte trafficking was demonstrated with the S1P(1)-selective nanomolar agonist, SEW2871. Despite its lack of charged headgroup, the tetraaromatic compound SEW2871 binds and activates S1P(1) through a combination of hydrophobic and ion-dipole interactions. Both S1P and SEW2871 activated ERK, Akt, and Rac signaling pathways and induced S1P(1) internalization and recycling, unlike FTY720-phosphate, which induces receptor degradation. Agonism with receptor recycling is sufficient for alteration of lymphocyte trafficking by S1P and SEW2871. S1P(1) modeling and mutagenesis studies revealed that residues binding the S1P headgroup are required for kinase activation by both S1P and SEW2871. Therefore, SEW2871 recapitulates the action of S1P in all the signaling pathways examined and overlaps in interactions with key headgroup binding receptor residues, presumably replacing salt-bridge interactions with ion-dipole interactions. 相似文献
12.
Diastereopure monofluorinated cyclopropanoid nucleosides were synthesized for biological studies. As key intermediates cis- and trans-(+/-)-[1-fluoro-2-(acetoxymethyl)cyclopropyl]methanol were prepared starting from diastereopure fluorinated cyclopropanecarboxylates. The latter were synthesized by copper(i)-catalyzed cyclopropanation of [small alpha]-fluorostyrene with ethyl diazoacetate. After reduction and O-acetylation the diastereomeric (2-fluoro-2-phenylcyclopropyl)methyl acetates were obtained. Oxidative degradation using RuO(4) and reduction of the formed carboxyl group with borane gave the fluorinated alcohols, which were coupled with different nucleobases. After deprotection, the corresponding cyclopropanoid nucleosides of adenine, cytosine, guanine, thymine and uracil were obtained. Antiviral tests revealed for the cis-configured guanosine a low, but specific activity against HSV-1 and HSV-2. In addition low affinities of the adenine derivatives to adenosine receptors were detected. 相似文献
13.
This work focuses on the RNA-protein interactions necessary for efficient aminoacylation of tRNAHis by Escherichia coli histidyl-tRNA synthetase (HisRS). The E. coli tRNAHis acceptor stem is characterized by a unique "extra" G-1:C73 base pair. Previous in vivo and in vitro studies showed that G-1:C73 is a major recognition element for E. coli HisRS. To further probe the role of the G-1:C73 base pair in specific aminoacylation, we carried out atomic group "mutagenesis" studies. Systematic base analogue substitutions at the -1:73 position of chemically synthesized microhelixHis substrates suggest that the G-1 base serves to position the 5'-monophosphate, which is critical for aminoacylation. Additionally, the C73 and G-1 bases contain major groove exocyclic atomic groups that contribute to HisRS recognition. 相似文献
14.
Tsai P Ichikawa K Mailer C Pou S Halpern HJ Robinson BH Nielsen R Rosen GM 《The Journal of organic chemistry》2003,68(20):7811-7817
Apparent rate constants, at acidic pH and neutral pH for the reaction of a family of ester-containing 5-carboxyl-5-methyl-1-pyrroline N-oxides with superoxide (O2*-) were estimated, using ferricytochrome c as a competitive inhibitor. It was of interest to note that the rate constants were similar among the different nitrones and not that significantly different from that found for 5-(diethoxyphosphoryl)-5-dimethyl-1-pyrroline N-oxide. At acidic pH, the rate constant for spin trapping O2*- was 3-fold greater than that at physiological pH. Subsequent experiments determined the half-life of aminoxyls, derived from the reaction of these nitrones with O2*-. The EPR spectra were modeled by using a global analysis method. The results clearly demonstrated that EPR spectra of all the aminoxyls were inconsistent with a model that included a single gamma-hydrogen splitting. A better interpretation modeled them as two diastereomers with identical nitrogen splittings and slightly different beta-hydrogen splittings. Detailed line width analyses slightly favored an equal line width-unequal population ratio for the two diastereomers. 相似文献
15.
W. A. Ludwico S. L. Rosen 《Journal of polymer science. Part A, Polymer chemistry》1976,14(9):2121-2134
The effect of dissolved polybutadiene on the initial rate of polymerization of styrene was investigated by using high-precision dilatometric techniques. The dissolved polymer reduced the rate of polymerization by amounts greater than can be accounted for by a reduction in monomer concentration. Rate reductions increased with the amount of dissolved polybutadiene and with its molecular weight and were greater for benzoyl peroxide initiator than for equal concentrations of azobisisobutyronitrile. Surprisingly, analogous rate reductions were observed when polystyrene were substituted for the polybutadienes, except that at high polystyrene concentrations, the expected autoacceleration was observed. These rate reductions showed no correlation with the viscosity of the reaction mass, nor did the dissolved polymer affect initiator efficiency. At a given level of a particular dissolved polybutadiene, rate reductions were diminished by increasing levels of each initiator, and by adding a chain-transfer agent. Good quantitative agreement was obtained with the number-average length of the growing polymer chains, whether varied by using different initiators, changing initiator level, or adding chain-transfer agent. These results are inconsistent with a chemical mechanism, but they are explained by a proposal originated by North and Reed whereby the dissolved polymer makes the reaction mass a “poorer” solvent for the growing polymer chains, reducing their overall coil dimensions and enhancing their rate of diffusion together for termination. 相似文献
16.
J. E. Rosen A. K. Prahalad† G. Schluter D. Chen G. M. Williams‡ 《Photochemistry and photobiology》1997,65(6):990-996
To study the basis for the phototoxicity of quinolones, a class of synthetic antibacterials, the photodynamic ability to mediate 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) formation in cultured cells was measured for lome-floxacin (LMX), which is strongly associated with clinical phototoxicity in humans, and ciprofloxacin (CFX), which has few reports of phototoxicity. Adult rat liver (ARL-18) cells were exposed to the quinolones in the presence of UVA and DNA was extracted and analyzed by HPLC with electrochemical detection. Low levels of 8-oxo-dG were found in the DNA of nonirradiated ARL-18 cells and this was increased up to 6-fold in the presence of either LMX (50–400 uAf) or up to 3.6-fold in the presence of CFX (50–400 µM) and UVA (20 J/cm2) when compared to the UVA control. Comparing separate experiments with LMX and CFX, LMX produced greater levels of 8-oxo-dG either after dark exposure or after UVA exposure at 20 J/cm2. Also, LMX and CFX were both shown to photodegrade in the presence of UVA, and it was determined that UVA photoinstability alone does not reflect phototoxic potential. These data suggest that the photodynamic potential of LMX and CFX to produce 8-oxo-dG may relate to their human clinical phototoxicity profile. We suggest that the observed clinical phototoxicity is mediated through a UVA photodynamic effect on the quinolone to form reactive oxygen species in the presence of molecular oxygen. The findings indicate that 8-oxo-dG formation can serve as a marker for the potential phototoxicity of new quinolones. 相似文献
17.
Mair RW Rosen MS Wang R Cory DG Walsworth RL 《Magnetic resonance in chemistry : MRC》2002,40(13):S29-S39
We report initial NMR studies of (i) xenon gas diffusion in model heterogeneous porous media and (ii) continuous flow laser-polarized xenon gas. Both areas utilize the pulsed gradient spin-echo (PGSE) techniques in the gas phase, with the aim of obtaining more sophisticated information than just translational self-diffusion coefficients--a brief overview of this area is provided in the Introduction. The heterogeneous or multiple-length scale model porous media consisted of random packs of mixed glass beads of two different sizes. We focus on observing the approach of the time-dependent gas diffusion coefficient, D(t) (an indicator of mean squared displacement), to the long-time asymptote, with the aim of understanding the long-length scale structural information that may be derived from a heterogeneous porous system. We find that D(t) of imbibed xenon gas at short diffusion times is similar for the mixed bead pack and a pack of the smaller sized beads alone, hence reflecting the pore surface area to volume ratio of the smaller bead sample. The approach of D(t) to the long-time limit follows that of a pack of the larger sized beads alone, although the limiting D(t) for the mixed bead pack is lower, reflecting the lower porosity of the sample compared to that of a pack of mono-sized glass beads. The Pade approximation is used to interpolate D(t) data between the short- and long-time limits. Initial studies of continuous flow laser-polarized xenon gas demonstrate velocity-sensitive imaging of much higher flows than can generally be obtained with liquids (20-200 mm s-1). Gas velocity imaging is, however, found to be limited to a resolution of about 1 mm s-1 owing to the high diffusivity of gases compared with liquids. We also present the first gas-phase NMR scattering, or diffusive-diffraction, data, namely flow-enhanced structural features in the echo attenuation data from laser-polarized xenon flowing through a 2 mm glass bead pack. 相似文献
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20.
Armstrong TA Bettoni D Bharadwaj V Biino C Borreani G Broemmelsiek D Buzzo A Calabrese R Ceccucci A Cester R Church M Dalpiaz P Dalpiaz PF Dimitroyannis D Fabbri M Fast J Gianoli A Ginsburg CM Gollwitzer K Govi G Hahn A Hasan M Hsueh S Lewis R Luppi E Macrí M Majewska AM Mandelkern M Marchetto F Marinelli M Marques J Marsh W Martini M Masuzawa M Menichetti E Migliori A Mussa R Palestini S Pallavicini M Passaggio S Pastrone N Patrignani C Peoples J Petrucci F Pia MG Pordes S Rapidis P Ray R 《Physical review D: Particles and fields》1996,54(11):7067-7070