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61.
Maksim V. Kvach Igor A. Prokhorenko Alexey V. Ustinov Sergei V. Gontarev Vladimir A. Korshun Vadim V. Shmanai 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):809-813
New reagents (CPGs and phosphoramidites) for automatic solid phase synthesis of modified oligonucleotides were designed. Three oligonucleotides carrying fluorescent label at the 5′-terminus and an anchor group at the 3′-terminus were prepared and their immobilization in orthogonal conditions on solid supports was studied. 相似文献
62.
Anu Arya Divya Mathur Abhilash Tyagi Rajesh Kumar Vinod Kumar Carl E. Olsen 《Nucleosides, nucleotides & nucleic acids》2013,32(12):646-659
An efficient protocol has been developed for the synthesis of a small library of 3′-deoxy-3′-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reaction of 3′-azido-3′-deoxy-5-methyluridine with different alkynes under optimized condition in an overall yields of 76%–92%. Here, the azido precursor compound, i.e., 3′-azido-3′-deoxy-5-methyluridine was chemoenzymatically synthesized from D-xylose in good yield. Some of the alkynes used in cycloaddition reaction were synthesized by the reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using K2CO3in excellent yields. All synthesized compounds were unambiguously identified on the basis of their spectral (IR, 1H-, 13C NMR spectra, and high-resolution mass spectra) data analysis. 相似文献
63.
Katharina L. Dürr Neslihan N. Tavraz Susan Spiller Thomas Friedrich 《Journal of visualized experiments : JoVE》2013,(72)
Whereas cation transport by the electrogenic membrane transporter Na+,K+-ATPase can be measured by electrophysiology, the electroneutrally operating gastric H+,K+-ATPase is more difficult to investigate. Many transport assays utilize radioisotopes to achieve a sufficient signal-to-noise ratio, however, the necessary security measures impose severe restrictions regarding human exposure or assay design. Furthermore, ion transport across cell membranes is critically influenced by the membrane potential, which is not straightforwardly controlled in cell culture or in proteoliposome preparations. Here, we make use of the outstanding sensitivity of atomic absorption spectrophotometry (AAS) towards trace amounts of chemical elements to measure Rb+ or Li+ transport by Na+,K+- or gastric H+,K+-ATPase in single cells. Using Xenopus oocytes as expression system, we determine the amount of Rb+ (Li+) transported into the cells by measuring samples of single-oocyte homogenates in an AAS device equipped with a transversely heated graphite atomizer (THGA) furnace, which is loaded from an autosampler. Since the background of unspecific Rb+ uptake into control oocytes or during application of ATPase-specific inhibitors is very small, it is possible to implement complex kinetic assay schemes involving a large number of experimental conditions simultaneously, or to compare the transport capacity and kinetics of site-specifically mutated transporters with high precision. Furthermore, since cation uptake is determined on single cells, the flux experiments can be carried out in combination with two-electrode voltage-clamping (TEVC) to achieve accurate control of the membrane potential and current. This allowed e.g. to quantitatively determine the 3Na+/2K+ transport stoichiometry of the Na+,K+-ATPase and enabled for the first time to investigate the voltage dependence of cation transport by the electroneutrally operating gastric H+,K+-ATPase. In principle, the assay is not limited to K+-transporting membrane proteins, but it may work equally well to address the activity of heavy or transition metal transporters, or uptake of chemical elements by endocytotic processes. 相似文献
64.
Derek D. Lovingood Jeffrey R. Owens Michael Seeber Konstantin G. Kornev Igor Luzinov 《Journal of visualized experiments : JoVE》2013,(82)
Microwave-assisted synthetic techniques were used to quickly and reproducibly produce silica nanoparticle sols using an acid catalyst with nanoparticle diameters ranging from 30-250 nm by varying the reaction conditions. Through the selection of a microwave compatible solvent, silicic acid precursor, catalyst, and microwave irradiation time, these microwave-assisted methods were capable of overcoming the previously reported shortcomings associated with synthesis of silica nanoparticles using microwave reactors. The siloxane precursor was hydrolyzed using the acid catalyst, HCl. Acetone, a low-tan δ solvent, mediates the condensation reactions and has minimal interaction with the electromagnetic field. Condensation reactions begin when the silicic acid precursor couples with the microwave radiation, leading to silica nanoparticle sol formation. The silica nanoparticles were characterized by dynamic light scattering data and scanning electron microscopy, which show the materials'' morphology and size to be dependent on the reaction conditions. Microwave-assisted reactions produce silica nanoparticles with roughened textured surfaces that are atypical for silica sols produced by Stöber''s methods, which have smooth surfaces. 相似文献
65.
Marianne Rooman Emilie Cauët Jacques Liévin René Wintjens 《Journal of biomolecular structure & dynamics》2013,31(6):949-954
Abstract Electron holes are known to migrate along the DNA or RNA duplexes and to localize preferentially on successive guanines. The stationary point conformations of Gua pairs that can trap or let pass these holes have been characterized by quantum chemistry calculations. Here we show their recurrent occurrence in DNA and RNA X-ray structures, often in quadruplex conformations or in interaction with proteins, ligands or metal ions. These findings give support to the biological, possibly regulatory, roles of charge migration in cell functioning. 相似文献
66.
Nathan L. Meyers Libo Wang Olga Gursky Donald M. Small 《Journal of lipid research》2013,54(7):1927-1938
Amphipathic α-helices mediate binding of exchangeable apolipoproteins to lipoproteins. To probe the role of α-helical structure in protein-lipid interactions, we used oil-drop tensiometry to characterize the interfacial behavior of apolipoprotein C-I (apoC-I) variants at triolein/water (TO/W) and 1-palmitoyl-2-oleoylphosphatidylcholine/triolein/water (POPC/TO/W) interfaces. ApoC-I, the smallest apolipoprotein, has two amphipathic α-helices. Mutants had single Pro or Ala substitutions that resulted in large differences in helical content in solution and on phospholipids. The ability of apoC-I to bind TO/W and POPC/TO/W interfaces correlated strongly with α-helical propensity. On binding these interfaces, peptides with higher helical propensity increased surface pressure to a greater extent. Likewise, peptide exclusion pressure at POPC/TO/W interfaces increased with greater helical propensity. ApoC-I retention on TO/W and POPC/TO/W interfaces correlated strongly with phospholipid-bound helical content. On compression of these interfaces, peptides with higher helical content were ejected at higher pressures. Substitution of Arg for Pro in the N-terminal α-helix altered net charge and reduced apoC-I affinity for POPC/TO/W interfaces. Our results suggest that peptide-lipid interactions drive α-helix binding to and retention on lipoproteins. Point mutations in small apolipoproteins could significantly change α-helical propensity or charge, thereby disrupting protein-lipid interactions and preventing the proteins from regulating lipoprotein catabolism at high surface pressures. 相似文献
67.
Plant fitness is affected by herbivory, and in moist tropical forests, 70 percent of herbivore damage occurs on young leaves. Thus, to understand the effects of herbivory on tropical plant fitness, it is necessary to understand how tropical young leaves survive the brief, but critical, period of susceptibility. In this study, we surveyed three species of Inga during young leaf expansion. Three classes of toxic secondary metabolites (phenolics, saponins, and tyrosine), extrafloral nectar production, leaf area, and extrafloral nectary area were measured at randomly assigned young leaf sizes. In addition, all defenses were compared for potential trade‐offs during leaf expansion. No trade‐offs among defenses were found, and the concentration of all defenses, except tyrosine, decreased during leaf expansion. We suggest that plants continued to increase phenolic and saponin content, but at a rate that resulted in decreasing concentrations. In contrast, tyrosine content per leaf steadily increased such that a constant concentration was maintained regardless of young leaf size. Nectar production remained constant during leaf expansion, but, because young leaf area increased by tenfold, the investment in extrafloral nectar per leaf area significantly decreased. In addition, nectary area did not change during leaf expansion and therefore the relative size of the nectary significantly decreased during young leaf expansion. These results support the predictions of the optimal defense hypothesis and demonstrate that the youngest leaves have the highest investment in multiple defenses, most likely because they have the highest nitrogen content and are most susceptible to a diversity of herbivores. 相似文献
68.
Emmanuel Deau Yvonnick Loidreau Pascal Marchand Marie-Renée Nourrisson Nadège Loaëc Laurent Meijer Vincent Levacher Thierry Besson 《Bioorganic & medicinal chemistry letters》2013,23(24):6784-6788
The efficient synthesis of 7-substituted pyrido[2′,3′:4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaffold was accomplished, before or after cyclisation step, by palladium-catalyzed Suzuki–Miyaura cross-coupling while the pyrimidin-4-amines and N-aryl counterparts were synthesized by microwave-assisted formamide degradation and Dimroth rearrangement, respectively. The final products were evaluated for their potent inhibition of a series of five Ser/Thr kinases (CDK5/p25, CK1δ/ε, CLK1, DYRK1A, GSK3α/β). Compound 35 showed the best inhibitory activity with an IC50 value of 49 nM and proved to be specific to CLK1 among the panel of tested kinases. 相似文献
69.
Steven R. LaPlante François Bilodeau Norman Aubry James R. Gillard Jeff O’Meara René Coulombe 《Bioorganic & medicinal chemistry letters》2013,23(16):4663-4668
A classic synthetic issue that remains unresolved is the reaction that involves the control of N- versus O-alkylation of ambident anions. This common chemical transformation is important for medicinal chemists, who require predictable and reliable protocols for the rapid synthesis of inhibitors. The uncertainty of whether the product(s) are N- and/or O-alkylated is common and can be costly if undetermined. Herein, we report an NMR-based strategy that focuses on distinguishing inhibitors and intermediates that are N- or O-alkylated. The NMR strategy involves three independent and complementary methods. However, any combination of two of the methods can be reliable if the third were compromised due to resonance overlap or other issues. The timely nature of these methods (HSQC/HMQC, HMBC. ROESY, and 13C shift predictions) allows for contemporaneous determination of regioselective alkylation as needed during the optimization of synthetic routes. 相似文献
70.
J. Adam Hendricks Robert N. Hanson Michael Amolins John M. Mihelcic Brian S. Blagg 《Bioorganic & medicinal chemistry letters》2013,23(12):3635-3639
Three novel steroidal antiestrogen–geldanamycin conjugates were prepared using a convergent strategy. The antiestrogenic component utilized the 11β-(4-functionalized-oxyphenyl) estradiol scaffold, while the geldanamycin component was derived by replacement of the 17-methoxy group with an appropriately functionalized amine. Ligation was achieved in high yield using azide alkyne cyclization reactions. Evaluation of the products against two breast cancer cell lines indicated that the conjugates retained significant antiproliferative activity. 相似文献