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101.
Mahinpour R Riazi G Shokrgozar MA Sarbolouki MN Ahmadian S Douraghi M Hadi Alijanvand H Azadmanesh K Heidari M Naghdi Gheshlaghi Z Moosavi-Movahedi AA 《Cell biology international》2012,36(4):403-408
Arsenical compounds exhibit a differential toxicity to cancer cells. Microtubules are a primary target of a number of anticancer drugs, such as arsenical compounds. The interaction of 1-NAA (1-naphthylarsonic acid) has been investigated on microtubule polymerization under in vitro and cellular conditions. Microtubules were extracted from sheep brain. Transmission electron microscopy was used to show microtubule structure in the presence of 1-NAA. Computational docking method was applied for the discovery of ligand-binding sites on the microtubular proteins. Proliferation of HeLa cells and HF2 (human foreskin fibroblasts) was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay method following their incubation with 1-NAA. Fluorescence microscopic labelling was done with the help of α-tubulin monoclonal antibody and Tunel kit was used to investigate the apoptotic effects of 1-NAA on the HeLa cells. 1-NAA inhibits the tubulin polymerization by the formation of abnormal polymers having high affinity to the inner cell wall. 相似文献
102.
Background
Nucleic acids based therapeutic approaches have gained significant interest in recent years towards the development of therapeutics against many diseases. Recently, research on aptamers led to the marketing of Macugen®, an inhibitor of vascular endothelial growth factor (VEGF) for the treatment of age related macular degeneration (AMD). Aptamer technology may prove useful as a therapeutic alternative against an array of human maladies. Considering the increased interest in aptamer technology globally that rival antibody mediated therapeutic approaches, a simplified selection, possibly in one-step, technique is required for developing aptamers in limited time period.Principal Findings
Herein, we present a simple one-step selection of DNA aptamers against α-bungarotoxin. A toxin immobilized glass coverslip was subjected to nucleic acid pool binding and extensive washing followed by PCR enrichment of the selected aptamers. One round of selection successfully identified a DNA aptamer sequence with a binding affinity of 7.58 µM.Conclusion
We have demonstrated a one-step method for rapid production of nucleic acid aptamers. Although the reported binding affinity is in the low micromolar range, we believe that this could be further improved by using larger targets, increasing the stringency of selection and also by combining a capillary electrophoresis separation prior to the one-step selection. Furthermore, the method presented here is a user-friendly, cheap and an easy way of deriving an aptamer unlike the time consuming conventional SELEX-based approach. The most important application of this method is that chemically-modified nucleic acid libraries can also be used for aptamer selection as it requires only one enzymatic step. This method could equally be suitable for developing RNA aptamers. 相似文献103.
Using first principle calculations, we investigated cation-π interactions between alkali cations (Li(+), Na(+), and K(+)) and pristine C(24) or doped fullerenes of BC(23), and NC(23). The most suitable adsorption site is found to be atop the center of a six-membered ring of the exterior surface of C(24) molecule. Interaction energies of these cations decreased in the order: Li(+)?>?Na(+)?>?K(+), with values of -31.82, -22.36, and -15.68 kcal mol(-1), respectively. It was shown that the interaction energies are increased and decreased by impurity doping of B and N atoms in adjacent wall of adsorption site, depending on electron donating or receptivity of the doping atoms. 相似文献
104.
The electro-oxidation of epinephrine (EP), uric acid (UA), folic acid (FA), and their mixture has been studied by modified carbon nanotube paste electrode of 2,2'-[1,2-ethanediylbis(nitriloethylidyne)]-bis-hydroquinone using cyclic voltammetry, chronoamperometry and differential pulse voltammetry. This modified electrode exhibited potent and persistent electron mediating behavior followed by well-separated oxidation peaks towards EP, UA and FA with activation overpotential. For the ternary mixture containing EP, UA and FA the three compounds can be well separated from each other at the scan rate of 20mVs(-1). The obtained catalytic peak current, was linearly dependent on the EP, UA and FA concentrations in the range of 0.7-1200muM, 25-750muM and 15-800muM and the detection limits for EP, UA and FA were 0.216+/-0.004, 8.8+/-0.2 and 11.0+/-0.3muM, respectively. The diffusion coefficient (D), and the kinetic parameters such as electron transfer coefficient, (alpha) and heterogeneous rate constant, (k') for EP were also determined using electrochemical approaches. The modified electrode showed good sensitivity, selectivity and stability, and was employed for the determination of EP, UA and FA in the real samples. 相似文献
105.
Peptidoglycan recycling is a process in which bacteria import cell wall degradation products and incorporate them back into either peptidoglycan biosynthesis or basic metabolic pathways. The enzyme MurQ is an N-acetylmuramic acid 6-phosphate (MurNAc 6-phosphate) hydrolase (or etherase) that hydrolyzes the lactyl side chain from MurNAc 6-phosphate and generates GlcNAc 6-phosphate. This study supports a mechanism involving the syn elimination of lactate to give an alpha,beta-unsaturated aldehyde with (E)-stereochemistry, followed by the syn addition of water to give product. The observation of both a kinetic isotope effect slowing the reaction of [2-(2)H]MurNAc 6-phosphate and the incorporation of solvent-derived deuterium into C2 of the product indicates that the C2-H bond is cleaved during catalysis. The observation that the solvent-derived (18)O isotope is incorporated into the C3 position of the product, but not the C1 position, provides evidence of the cleavage of the C3-O bond and argues against imine formation. The finding that 3-chloro-3-deoxy-GlcNAc 6-phosphate serves as an alternate substrate is also consistent with an elimination-addition mechanism. Upon extended incubations of MurQ with GlcNAc 6-phosphate, the alpha,beta-unsaturated aldehydic intermediate accumulates in solution, and (1)H NMR analysis indicates it exists as the ring-closed form of the (E)-alkene. A structural model is developed for the Escherichia coli MurQ and is compared to that of the structural homologue glucosamine-6-phosphate synthase. Putative active site acid/base residues are probed by mutagenesis, and Glu83 and Glu114 are found to be crucial for catalysis. The Glu83Ala mutant is essentially inactive as an etherase yet is capable of exchanging the C2 proton of substrate with solvent-derived deuterium. This suggests that Glu83 may function as the acidic residue that protonates the departing lactate. 相似文献
106.
Duringan August, 1999 field campaign, measurements were made to establish hydrologicoptical properties of the Hudson/Raritan Estuary (New York-New Jersey): 1)concurrent above-and below-surface spectral irradiance; 2) sampling forlaboratory determination of inherent optical properties; and 3) concentrationsof optically-important water quality parameters. We used a bio optical modelbased on to predict thesubsurface irradiance reflectance from optically important water constituents.This model was then validated with the measured reflectance spectra from thefield spectroradiometers. Modeling of reflectance is a prerequisite forprocessing remote sensing data to desired thematic maps. These are key input tothe geographic information system (GIS) used to manage the water qualitycondition of the estuary. 相似文献
107.
Hanieh Bagheri Tudashki Youssef Haddad Iness Charfi Rejean Couture Graciela Pineyro 《Journal of cellular and molecular medicine》2020,24(10):5718-5730
δ-opioid receptor (DOPr) agonists have analgesic efficacy in chronic pain models but development of tolerance limits their use for long-term pain management. Although agonist potential for inducing acute analgesic tolerance has been associated with distinct patterns of DOPr internalization, the association between trafficking and chronic tolerance remains ill-defined. In a rat model of streptozotocin (STZ)-induced diabetic neuropathy, deltorphin II and TIPP produced sustained analgesia following daily (intrathecal) i.t. injections over six days, whereas similar treatment with SNC-80 or SB235863 led to progressive tolerance and loss of the analgesic response. Trafficking assays in murine neuron cultures showed no association between the magnitude of ligand-induced sequestration and development of chronic tolerance. Instead, ligands that supported DOPr recycling were also the ones producing sustained analgesia over 6-day treatment. Moreover, endosomal endothelin-converting enzyme 2 (ECE2) blocker 663444 prevented DOPr recycling by deltorphin II and TIPP and precipitated tolerance by these ligands. In conclusion, agonists, which support DOPr recycling, avoid development of analgesic tolerance over repeated administration. 相似文献
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