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Sample records for ferrocene labeled nucleosides

  1. Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

    Directory of Open Access Journals (Sweden)

    Kois Pavol

    2006-11-01

    Full Text Available Abstract Background Reaction of azides with triaryl phosphines under mild conditions gives iminophosphoranes which can react with almost any kind of electrophilic reagent, e.g. aldehydes/ketones to form imines or esters to form amides. This so-called Staudinger ligation has been employed in a wide range of applications as a general tool for bioconjugation including specific labeling of nucleic acids. Results A new approach for the preparation of labeled nucleosides via intermolecular Staudinger ligation is described. Reaction of azidonucleosides with triphenylphosphine lead to iminophosphorane intermediates, which react subsequently with derivatives of coumarin or ferrocene to form coumarin or ferrocene labeled nucleosides. Fluorescent properties of coumarin labeled nucleosides are determined. Conclusion New coumarin and ferrocene labeled nucleosides were prepared via intermolecular Staudinger ligation. This reaction joins the fluorescent coumarin and biospecific nucleoside to the new molecule with promising fluorescent and electrochemical properties. The isolated yields of products depend on the structure of azidonucleoside and carboxylic acids. A detailed study of the kinetics of the Staudinger ligation with nucleoside substrates is in progress.

  2. Synthesis of tritium labelled nucleoside triphosphates by enzymatic phosphorylation

    International Nuclear Information System (INIS)

    Shen Decun; Ji Linzhen; Liao Sha

    1986-01-01

    [5- 3 H]UMP, [5- 3 H]CMP, [8- 3 H]AMP and [8- 3 H]GMP were prepared from 5BrUMP 5BrCMP 8BrAMP and 8BrGMP by catalytic halogentritium replacement at the same time. [5- 3 H]UTP, [5- 3 H]CTP, [8- 3 H]ATP and [8- 3 H]GTP were subsequently synthesized from [5- 3 H]UMP, [5- 3 H]CMP, [8- 3 H]AMP and [8- 3 H]GMP by enzymatic phosphorylation with the crude enzyme prepared from brewer's yeasts and purified by paper chromatography simultaneously. In addition, four kinds of tritium labelled nucleoside monophosphates and four kinds of tritium labelled nucleoside diphosphates were obtained as the by-products. The specific activity of these products is between 14-19 Ci/mmol and the radiochemical purity is more than 98%

  3. Efficient method of enzymatic synthesis of nucleosides labelled with 14C and 3H

    International Nuclear Information System (INIS)

    Nejedly, Z.; Filip, J.

    1988-01-01

    The method is presented of enzymatic synthesis of nucleosides labelled with 14 C or 3 H either uniformly or specifically in the base or the deoxyribosyl or ribosyl moiety. The method is based on the ribosylation or deoxyribosylation of the nucleic acid bases (non-labelled or labelled with 14 C or 3 H) by the catalytic effect of enzymes occurring in the supernatant fractions of non-purified homogenates of Escherichia coli B. bacteria. The non-labelled and labelled nucleosides are used as donors of ribosyl or deoxyribosyl groups. The HPLC method is used for separating labelled nucleosides. The radiochemical purity of the labelled nucleosides is higher than 98%, molar activity ranges from 9.2 to 18.5 GBq.mmol -1 ( 14 C-labelled compounds) and from 0.6 to 1.9 TBq.mmol -1 (3H-labelled compounds). (author). 4 figs., 8 refs

  4. Ferrocene, ruthenocene or rhodocene analogues of Haloperidol. Synthesis and organ distribution after labelling with 103Ru or 103mRh

    International Nuclear Information System (INIS)

    Wenzel, M.; Wu, Y.

    1988-01-01

    Ferrocene-Haloperidol was synthesized by N-alkylation of 4-(4'-chlorophenyl)-4-hydroxypiperidine with 1-ferrocenyl-4-chlor-butan-1-on. By heating the ferrocene-haloperidol with 103 RuCl 3 the 103 Ru-labelled ruthenocene-haloperidol was obtained. This compound showed a high affinity for lung but not for brain in rats and mice. The decay of the 103 Ru labelled compound results in the formation of the 103m Rh labelled rhodocene-haloperidol, which is rapidly oxidized by air to the corresponding rhodocinium-haloperidol. This compound can be separated by extraction and TLC. (author)

  5. Ferrocene, ruthenocene or rhodocene analogues of Haloperidol. Synthesis and organ distribution after labelling with /sup 103/Ru or /sup 103m/Rh

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, M; Wu, Y

    1988-01-01

    Ferrocene-Haloperidol was synthesized by N-alkylation of 4-(4'-chlorophenyl)-4-hydroxypiperidine with 1-ferrocenyl-4-chlor-butan-1-on. By heating the ferrocene-haloperidol with /sup 103/RuCl/sub 3/ the /sup 103/Ru-labelled ruthenocene-haloperidol was obtained. This compound showed a high affinity for lung but not for brain in rats and mice. The decay of the /sup 103/Ru labelled compound results in the formation of the /sup 103m/Rh labelled rhodocene-haloperidol, which is rapidly oxidized by air to the corresponding rhodocinium-haloperidol. This compound can be separated by extraction and TLC.

  6. Complete inactivation of HIV-1 using photo-labeled non-nucleoside reverse transcriptase inhibitors.

    Science.gov (United States)

    Rios, Adan; Quesada, Jorge; Anderson, Dallas; Goldstein, Allan; Fossum, Theresa; Colby-Germinario, Susan; Wainberg, Mark A

    2011-01-01

    We demonstrate that a photo-labeled derivative of the non-nucleoside reverse transcriptase inhibitor (NNRTI) dapivirine termed DAPY, when used together with exposure to ultraviolet light, was able to completely and irreversibly inactivate both HIV-1 RT activity as well as infectiousness in each of a T cell line and peripheral blood mononuclear cells. Control experiments using various concentrations of DAPY revealed that a combination of exposure to ultraviolet light together with use of the specific, high affinity photo-labeled compound was necessary for complete inactivation to occur. This method of HIV RT inactivation may have applicability toward preservation of an intact viral structure and warrants further investigation in regard to the potential of this approach to elicit a durable, broad protective immune response. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Evaluation of technetium-99m/rhenium labelled nucleoside analogues as potential radiotracers in oncology

    International Nuclear Information System (INIS)

    Desbouis, D.

    2007-01-01

    cell uptake in transfected cancer cells this technetium thymidine complex revealed a low internalisation of 0.03 ± 0.01%ID/(mg/mL). Under the same conditions the [ 3 H]thymidine exhibited an uptake of 1.50 ± 0.02%lD/(mg/mL). In order to gain potency and selectivity for HSV1-TK, the corresponding 5'-carboxamide 5-ethyl-2', 5'-dideoxyuridine was synthesized. The synthesis of the ligand was performed in seven steps from 2'-deoxyuridine. This ligand was then successfully labelled with the fac-M(CO) 3 -core (M = 99m Tc, Re). The rhenium complex was found to be a selective competitive inhibitor of HSV1-TK (K i = 4.56 ± 0.11 μM). Although the cellular uptake of the technetium 2'-deoxyurine complex (0.10 ± 0.01%ID/(mg/mL)) was better than its corresponding technetium thymidine complex, it is still very low compared to thymidine uptake. The second aspect of this work was to develop nucleoside derivatives labelled with technetium-99m/rhenium tricarbonyl core capable of acting as substrates for human cytosolic thymidine kinase (hTKl). hTKl is a target of choice to evaluate cell proliferation due to its overexpression in a variety of cancer cells. [ 18 F]Fluorothymidine [ 18 F]FLT), which acts as a hTKl substrate, has emerged as a very efficient PET tracer for the monitoring of cell proliferation. Our aim was to develop a SPET tracer with the same mode of action as [ 18 F]FLT. We prepared a set of technetium-99m/rhenium complexes of N3 thymidine derivatives with different overall charges (+1, 0 and -1) and variable spacer lengths. The complexes with different overall charges had the same spacer length between chelating system and thymidine moiety (two carbons spacer) while the complexes with different spacer lengths (2, 3, 5 and 10) were all neutral. These compounds were tested for their substrate activity with respect to recombinant hTKl. The phosphorylation rates of neutral and negative complexes were found to be similar, ranging between 15-16% with respect to thymidine

  8. Fluorinase: a tool for the synthesis of ¹⁸F-labeled sugars and nucleosides for PET.

    Science.gov (United States)

    Onega, Mayca; Winkler, Margit; O'Hagan, David

    2009-08-01

    There is an increasing interest in the preparation of (18)F-labeled radiopharmaceuticals with potential applications in PET for medicinal imaging. Appropriate synthetic methods require a quick and efficient route in which to incorporate the (18)F into a ligand, due to the relatively short half-life of the (18)F isotope. Enzymatic methods are rare in this area; however, the discovery of a fluorinating enzyme from Streptomyces cattleya (EC 2.5.1.63) has opened up the possibility of the enzymatic synthesis and formation of C-(18)F bonds from the [(18)F]fluoride ion. In this article, the development of enzymatic preparations of (18)F-labeled sugars and nucleosides as potential radiotracers using the fluorinase from S. cattleya for PET applications is reviewed. Enzymatic reactions are not traditional in PET synthesis, but this enzyme has some attractive features. The enzyme is available in an overexpressed form from Escherichia coli and it is relatively stable and can be easily purified and manipulated. Most notably, it utilizes [(18)F] fluoride, the form of the isotope normally generated by the cyclotron and usually in very high specific radioactivity. The disadvantage with the enzyme is that it is substrate specific; however, when the fluorinase is used in combination biotransformations with a second or third enzyme, then a range of radiolabeled nucleosides and ribose sugars can be prepared. The fluorinase enzyme has emerged as a curiosity from biosynthesis studies, but it now has some potential as a new catalyst for (18)F incorporation for PET syntheses. The focus is now on delivering a user-friendly catalyst to the PET synthesis community and establishing a clinical role for some of the (18)F-labeled molecules available using this technology.

  9. Evaluation of localized bacterial infection using radioisotope-labeled nucleosides imaging modality

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Su Jin; Kang, Joo Hyun; Lee, Yong Jin; Lee, Tae Sup; Kim, Kwang Il; Lee, Kyo Chul; An, Gwang II; Cheon, Gi Jeong; Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of); Lim, Sang Yong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    Conventional diagnostic methods for infections are difficult to distinguish localized bacterial infections from sites of sterile inflammation. For this reason, the importance of developing methods to image bacterial infections is widely recognized. In this study to acquire bacterial infection imaging with radiolabeled nucleosides, in vitro bacterial thymidine kinase (tk) activities of Salmonella typhimurium with [{sup 18}F]FLT and [{sup 125}I]IVDU were measured and localized infections model in BALB/c mice was imaged with [{sup 18}F]FLT or [{sup 125}I]FIAU

  10. Stable-isotope-labeled carbohydrates and nucleosides: Synthesis and applications in chemistry and biology

    International Nuclear Information System (INIS)

    Serianni, A.S.

    1994-01-01

    Carbohydrates play important roles in many key biochemical processes in living cells. For example, they are metabolized to produce energy, mediate cell-cell recognition, and play an indirect role (as constituents of DNA and RNA) in DNA replication, RNA transcription, and protein synthesis. These roles, and others of comparable biochemical significance, have been studied to varying extends with the use of stable isotopically labeled molecules, usually in conjunction with NMR spectroscopy and/or mass spectrometry. For example, carbohydrate metabolism has been monitored in vitro and in vivo with the use of isotopically labeled compounds. Molecular aspects of cell-cell recognition, mediated by cell-surface glycoproteins and glycolipids, have been probed through NMR studies of isotopically labeled oligosaccharides. More recently, the solution behavior of DNA and RNA has been examined through the use of labeled oligonucleotides. In all of these pursuits, the effort and expense to prepare labeled molecules, both of which can be substantial, are more than offset by the wealth of information derived from these studies. This information often cannot be accessed, or can be accessed only with great difficulty, using natural (unlabeled) compounds

  11. Stable-isotope-labeled carbohydrates and nucleosides: Synthesis and applications in chemistry and biology

    Energy Technology Data Exchange (ETDEWEB)

    Serianni, A.S. [Univ. of Notre Dame, IN (United States)

    1994-12-01

    Carbohydrates play important roles in many key biochemical processes in living cells. For example, they are metabolized to produce energy, mediate cell-cell recognition, and play an indirect role (as constituents of DNA and RNA) in DNA replication, RNA transcription, and protein synthesis. These roles, and others of comparable biochemical significance, have been studied to varying extends with the use of stable isotopically labeled molecules, usually in conjunction with NMR spectroscopy and/or mass spectrometry. For example, carbohydrate metabolism has been monitored in vitro and in vivo with the use of isotopically labeled compounds. Molecular aspects of cell-cell recognition, mediated by cell-surface glycoproteins and glycolipids, have been probed through NMR studies of isotopically labeled oligosaccharides. More recently, the solution behavior of DNA and RNA has been examined through the use of labeled oligonucleotides. In all of these pursuits, the effort and expense to prepare labeled molecules, both of which can be substantial, are more than offset by the wealth of information derived from these studies. This information often cannot be accessed, or can be accessed only with great difficulty, using natural (unlabeled) compounds.

  12. Labelling of nucleosides and oligonucleotides by solvatochromic 4-aminophthalimide fluorophore for studying DNA–protein interactions

    Czech Academy of Sciences Publication Activity Database

    Riedl, Jan; Pohl, Radek; Ernsting, N. P.; Orság, Petr; Fojta, Miroslav; Hocek, Michal

    2012-01-01

    Roč. 3, č. 9 (2012), s. 2797-2806 ISSN 2041-6520 R&D Projects: GA ČR GA203/09/0317; GA ČR GBP206/12/G151 Institutional support: RVO:61388963 ; RVO:68081707 Keywords : DNA * oligonucleotides * polymerase * phthalimide * nucleotides * fluorescent labeling Subject RIV: CC - Organic Chemistry Impact factor: 8.314, year: 2012

  13. Anthraquinone as a Redox Label for DNA: Synthesis, Enzymatic Incorporation, and Electrochemistry of Anthraquinone-Modified Nucleosides, Nucleotides, and DNA

    Czech Academy of Sciences Publication Activity Database

    Balintová, Jana; Pohl, Radek; Horáková Brázdilová, Petra; Vidláková, Pavlína; Havran, Luděk; Fojta, Miroslav; Hocek, Michal

    2011-01-01

    Roč. 17, č. 50 (2011), s. 14063-14073 ISSN 0947-6539 R&D Projects: GA MŠk(CZ) LC06035; GA MŠk LC512; GA AV ČR(CZ) IAA400040901 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : anthraquinone * DNA * electrochemistry * nucleosides * oligonucleotides Subject RIV: CC - Organic Chemistry Impact factor: 5.925, year: 2011

  14. Evaluation of technetium-99m/rhenium labelled nucleoside analogues as potential radiotracers in oncology[Dissertation 17173

    Energy Technology Data Exchange (ETDEWEB)

    Desbouis, D

    2007-07-01

    }M). This compound also exhibited a mixed inhibition of the hTK1 with K{sub ic} = 73 {+-} 20 {mu}M. When tested in vitro for cell uptake in transfected cancer cells this technetium thymidine complex revealed a low internalisation of 0.03 {+-} 0.01%ID/(mg/mL). Under the same conditions the [{sup 3}H]thymidine exhibited an uptake of 1.50 {+-} 0.02%lD/(mg/mL). In order to gain potency and selectivity for HSV1-TK, the corresponding 5'-carboxamide 5-ethyl-2', 5'-dideoxyuridine was synthesized. The synthesis of the ligand was performed in seven steps from 2'-deoxyuridine. This ligand was then successfully labelled with the fac-M(CO){sub 3}-core (M = {sup 99m}Tc, Re). The rhenium complex was found to be a selective competitive inhibitor of HSV1-TK (K{sub i} = 4.56 {+-} 0.11 {mu}M). Although the cellular uptake of the technetium 2'-deoxyurine complex (0.10 {+-} 0.01%ID/(mg/mL)) was better than its corresponding technetium thymidine complex, it is still very low compared to thymidine uptake. The second aspect of this work was to develop nucleoside derivatives labelled with technetium-99m/rhenium tricarbonyl core capable of acting as substrates for human cytosolic thymidine kinase (hTKl). hTKl is a target of choice to evaluate cell proliferation due to its overexpression in a variety of cancer cells. [{sup 18}F]Fluorothymidine [{sup 18}F]FLT), which acts as a hTKl substrate, has emerged as a very efficient PET tracer for the monitoring of cell proliferation. Our aim was to develop a SPET tracer with the same mode of action as [{sup 18}F]FLT. We prepared a set of technetium-99m/rhenium complexes of N3 thymidine derivatives with different overall charges (+1, 0 and -1) and variable spacer lengths. The complexes with different overall charges had the same spacer length between chelating system and thymidine moiety (two carbons spacer) while the complexes with different spacer lengths (2, 3, 5 and 10) were all neutral. These compounds were tested for their

  15. Negative ion electrospray ionization mass spectrometry of nucleoside phosphoramidate monoesters: elucidation of novel rearrangement mechanisms by multistage mass spectrometry incorporating in-source deuterium labelling.

    Science.gov (United States)

    Xu, Peng-Xiang; Hu, An-Fu; Hu, Dan; Gao, Xiang; Zhao, Yu-Fen

    2008-10-01

    Several O-2',3'-isopropylideneuridine-O-5'-phosphoramidate monoesters were synthesized and analyzed by negative ion electrospray ionization tandem mass spectrometry (ESI-MS(n)). Two kinds of novel rearrangement reactions were observed due to the difference in the amino acid in the nucleoside phosphoramidate monoesters, and possible mechanisms were proposed. One involves a five-membered cyclic transition state. The other is formation of a stable five-membered ring intermediate by Michael addition. Results were confirmed by tandem mass spectrometry and isotopically labeled hydrogen atoms. Furthermore, the internal hydrogen exchange between active hydrogen and methyl acrylate in the heated capillary of the mass spectrometer was found. The characteristic fragmentation behavior in ESI-MS may be used to monitor this kind of compounds in the biological metabolism.

  16. Anthraquinone as a redox label for DNA. Synthesis, enzymatic incorporation and electrochemistry of anthraquinone modified nucleosides, nucleotides and DNA

    Czech Academy of Sciences Publication Activity Database

    Balintová, J.; Havran, Luděk; Fojta, Miroslav; Hocek, Michal

    2012-01-01

    Roč. 106, - (2012), s1033-s1033 ISSN 0009-2770. [EuCheMS Chemistry Congress /4./. 26.08.2012-30.08.2012, Prague] R&D Projects: GA ČR GA203/09/0317; GA MŠk LC512; GA MŠk 1M0508; GA AV ČR(CZ) IAA400040901 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50040702 Keywords : nucleosides * oligonucleotides * electrochemistry Subject RIV: CC - Organic Chemistry

  17. Immobilization of ferrocene-modified SNAP-fusion proteins

    NARCIS (Netherlands)

    Wasserberg, D.; Uhlenheuer, D.; Neirynck, P.; Neirynck, Pauline; Cabanas Danés, Jordi; Schenkel, J.H.; Ravoo, B.J.; An, Q.; Huskens, Jurriaan; Milroy, L.G.; Brunsveld, Luc; Jonkheijm, Pascal

    2013-01-01

    The supramolecular assembly of proteins on surfaces has been investigated via the site-selective incorporation of a supramolecular moiety on proteins. To this end, fluorescent proteins have been site-selectively labeled with ferrocenes, as supramolecular guest moieties, via SNAP-tag technology. The

  18. Anomalous photoconductivity of ferrocene

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, A K [Indian Association for the Cultivation of Science, Calcutta (India). Dept. of Spectroscopy; Mallik, B [Indian Association for the Cultivation of Science, Calcutta (India). Dept. of Spectroscopy

    1995-08-15

    Photoconductivity behaviour of ferrocene, a very useful metallo-organic sandwich compound, has been investigated at different constant temperatures using powdery material in a sandwich type of cell configuration and with the exposure of a polychromatic light source (mercury lamp of 125 W). Measurements with a constant d.c. bias voltage (27 V) across the sample cell and a fixed intensity of the exciting light source have shown a drastic change in the photocurrent versus time profile with the increase in temperature. Anomalous changes have been observed in the plot of the photocurrent versus reciprocal of temperature. Such changes are completely absent in the corresponding dark current behaviour. The photoinduced changes have been observed to be almost reversible in the entire temperature range. In a particular temperature range the reversibility of photocurrent is accompanied by fluctuations in equilibrium current obtained after switching off the light source. The observed anomalous changes in photocurrent have been explained by photoinduced phase transition in ferrocene. The possible origin and implications of this photoinduced phase transition are discussed. (orig.)

  19. Organometallic and Bioorganometallic Chemistry - Ferrocene and Metal Carbonyls

    Directory of Open Access Journals (Sweden)

    Čakić Semenčić, M.

    2011-02-01

    procedure to use metal atoms in organometallics as labelling agents for antigens (A in immunoassays (IA is called metalloimmunoassay (MIA, Cais, 1977. Carbonyl metalloimmunoassay (CMIA is a heterogeneous competitive-type MIA using M-CO complexes as tracers, and FT-IR spectroscopy for quantification. This procedure allowed the simultaneous multiple IA reaching the fentomole concentration (Jaouen, 2000. From the variety of bioorganometallics synthesis and properties of the simple ferrocene-amino acids/peptides conjugates and ferrocene labelled carbohydrates, as well as the structure and function determination of B12 vitamin are described in this review.

  20. Nucleotides, Nucleosides, and Nucleobases

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank; Dandanell, Gert; Hove-Jensen, Bjarne

    2008-01-01

    We review literature on the metabolism of ribo- and deoxyribonucleotides, nucleosides, and nucleobases in Escherichia coli and Salmonella,including biosynthesis, degradation, interconversion, and transport. Emphasis is placed on enzymology and regulation of the pathways, at both the level of gene...

  1. Moessbauer study of tetramethylene bridged ferrocene derivatives Pt. 2

    International Nuclear Information System (INIS)

    Nagy, A.G.; Hillman, M.

    1978-01-01

    Suppositions for the molecular structure of trimethylene bridged ferrocene derivatives, i.e. for the tilt of cyclopentadienyl-rings and shortening of iron-ring distance, were supported by Moessbauer spectroscopic studies. The Moessbauer spectra of 1,1'-tetramethyleneferrocene and 1,1',3,3'-bis(tetramethylene)ferrocene were recorded by means of a constant acceleration type spectrometer using a 57 Co source in a chromium matrix. Simultaneous X-ray analysis of 1,1',3,3'-bis(trimethylene)ferrocene and 1,1',2,2',4,4'-tris(trimethylene)ferrocene confirmed the suppositions. (D.P.)

  2. Chiral ferrocenes in asymmetric catalysis: synthesis and applications

    National Research Council Canada - National Science Library

    Dai, Li-Xin; Hou, Xue-Long

    2010-01-01

    .... It provides a thorough overview of the synthesis and characterization of different types of chiral ferrocene ligands, their application to various catalytic asymmetric reactions, and versatile chiral...

  3. One-electron oxidations of ferrocenes: a pulse radiolysis study

    International Nuclear Information System (INIS)

    Faraggi, Moshe; Weinraub, Dany; Broitman, Federico; DeFelippis, M.R.; Klapper, M.H.

    1988-01-01

    Using the pulse radiolysis technique we have studied the oxidation by various inorganic radicals of four water soluble ferrocene derivatives, hydroxyethyl, dimethylaminomethyl, monocarboxylic acid and dicarboxylic acid. We report the second order rate constants for these reactions, the stabilities and spectral properties of the ferrocinium products, and the electrochemically determined ferrocinium/ferrocene redox potentials. We also present preliminary estimates of tyrosine and tryptophan radical redox potentials obtained with the dicarboxylic acid ferrocene derivative as reference, and we discuss the relationship between redox potential differences and the reactivities of the ferrocenes with the inorganic radicals. (author)

  4. Ferrocene-Functionalized Graphene Oxide Nanosheets: Efficient Electronic Communication between Ferrocene Centers across Graphene Nanosheets

    International Nuclear Information System (INIS)

    Lu, Yizhong; Jiang, Yuanyuan; Wu, Haibin; Chen, Wei

    2015-01-01

    Highlights: • Graphene oxide (GO) nanosheets functionalized with ferrocenyl moieties (GO-Fc) are fabricated. • GO-Fc shows efficient electronic communication between ferrocene centers. • GO-Fc exhibits two pairs of voltammetric peaks with a large potential spacing of 0.515 V. • GO-Fc shows a broad absorption peak in the near-infrared range (∼ 1428 nm) at mixed valence. - Abstract: Graphene oxide (GO) nanosheets functionalized with ferrocenyl moieties (GO-Fc) were fabricated through strong covalent C−C bonds. The resulting hybrid showed efficient electronic communication between ferrocene centers due to the strong electron delocalization facilitated by the large pi-pi conjugated structure of graphene sheets. The obtained hybrid exhibited two pairs of voltammetric peaks with a large potential spacing of 0.515 V and a broad absorption peak in the near-infrared range (∼ 1428 nm) at mixed valence. The electrochemical and near IR spectroscopic features suggested a Class II/III behavior of the intervalence charge transfer. This work indicates clearly that strong electronic coupling between ferrocene centers can be easily realized across graphene nanosheets with sp 2 -hybridized carbon

  5. Potentiometric and amperometric titration of ferrocene by cerium(4)

    International Nuclear Information System (INIS)

    Solomatin, V.T.

    1985-01-01

    Redox-potentials (E) of ferrocene (ferricenium-cation), Ce(4)/Ce(3) pairs are investigated and a possibility of regulating E value of these systems depending on the composition of water-organic media is shown. E value of Ce(4)/Ce(3) system decreases as increasing H 2 SO 4 concentration and CH 3 COOH mol share in the water-organic phase. Kinetic investigations of Ce(4)-ferrocene reactions shown that E constant value is achieved in 12-16 s depending on donor-acceptor properties of the solvent. Optimum conditions are chosen for potentiometric and amperometric titration of ferrocene by ceruium (4) in technological products. The method is versatile and permits to determine from tenths to dozens per cent of ferrocene

  6. Ferrocene Orientation Determined Intramolecular Interactions Using Energy Decomposition Analysis

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2015-11-01

    Full Text Available Two very different quantum mechanically based energy decomposition analyses (EDA schemes are employed to study the dominant energy differences between the eclipsed and staggered ferrocene conformers. One is the extended transition state (ETS based on the Amsterdam Density Functional (ADF package and the other is natural EDA (NEDA based in the General Atomic and Molecular Electronic Structure System (GAMESS package. It reveals that in addition to the model (theory and basis set, the fragmentation channels more significantly affect the interaction energy terms (ΔE between the conformers. It is discovered that such an interaction energy can be absorbed into the pre-partitioned fragment channels so that to affect the interaction energies in a particular conformer of Fc. To avoid this, the present study employs a complete fragment channel—the fragments of ferrocene are individual neutral atoms. It therefore discovers that the major difference between the ferrocene conformers is due to the quantum mechanical Pauli repulsive energy and orbital attractive energy, leading to the eclipsed ferrocene the energy preferred structure. The NEDA scheme further indicates that the sum of attractive (negative polarization (POL and charge transfer (CL energies prefers the eclipsed ferrocene. The repulsive (positive deformation (DEF energy, which is dominated by the cyclopentadienyle (Cp rings, prefers the staggered ferrocene. Again, the cancellation results in a small energy residue in favour of the eclipsed ferrocene, in agreement with the ETS scheme. Further Natural Bond Orbital (NBO analysis indicates that all NBO energies, total Lewis (no Fe and lone pair (LP deletion all prefer the eclipsed Fc conformer. The most significant energy preferring the eclipsed ferrocene without cancellation is the interactions between the donor lone pairs (LP of the Fe atom and the acceptor antibond (BD* NBOs of all C–C and C–H bonds in the ligand, LP(Fe-BD*(C–C & C

  7. Nucleoside Inhibitors of Zika Virus

    Czech Academy of Sciences Publication Activity Database

    Eyer, L.; Nencka, Radim; Huvarová, I.; Palus, Martin; Alves, M. J.; Gould, E. A.; De Clercq, E.; Růžek, Daniel

    2016-01-01

    Roč. 214, č. 5 (2016), s. 707-711 ISSN 0022-1899 Institutional support: RVO:61388963 ; RVO:60077344 Keywords : Zika virus * flavivirus * nucleoside analogue * antiviral * therapy Subject RIV: CC - Organic Chemistry; EE - Microbiology, Virology (BC-A) Impact factor: 6.273, year: 2016

  8. Ferrocene-functionalized graphene electrode for biosensing applications

    Energy Technology Data Exchange (ETDEWEB)

    Rabti, Amal [Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona (Spain); Université de Tunis El–Manar, Faculté des Sciences de Tunis, Laboratoire de Chimie Analytique et Electrochimie (LR99ES15), Campus universitaire de Tunis El–Manar, 2092, Tunis (Tunisia); Mayorga-Martinez, Carmen C.; Baptista-Pires, Luis [Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona (Spain); Raouafi, Noureddine, E-mail: n.raouafi@fst.rnu.tn [Université de Tunis El–Manar, Faculté des Sciences de Tunis, Laboratoire de Chimie Analytique et Electrochimie (LR99ES15), Campus universitaire de Tunis El–Manar, 2092, Tunis (Tunisia); Merkoçi, Arben, E-mail: arben.merkoci@icn2.cat [Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona (Spain); ICREA, Barcelona, Catalonia (Spain)

    2016-07-05

    A novel ferrocene-functionalized reduced graphene oxide (rGO)-based electrode is proposed. It was fabricated by the drop casting of ferrocene-functionalized graphene onto polyester substrate as the working electrode integrated within screen-printed reference and counter electrodes. The ferrocene-functionalized rGO has been fully characterized using FTIR, XPS, contact angle measurements, SEM and TEM microscopy, and cyclic voltammetry. The XPS and EDX analysis showed the presence of Fe element related to the introduced ferrocene groups, which is confirmed by a clear CV signal at ca. 0.25 V vs. Ag/AgCl (0.1 KCl). Mediated redox catalysis of H{sub 2}O{sub 2} and bio-functionalization with glucose oxidase for glucose detection were achieved by the bioelectrode providing a proof for potential biosensing applications. - Graphical abstract: An easy-to-prepare standalone graphene electrode was obtained by the drop-casting ferrocene-functionalized rGO on PET polymer. This electrode can be used as an enzymeless electrochemical sensor for the detection of hydrogen peroxide or as an amperometric enzyme-based biosensor for sensitive glucose detection. - Highlights: • A novel ferrocene-functionalized reduced graphene oxide based electrode. • Ease of preparation by drop-casting of Fc-modified graphene and chitosan mixture. • Well-defined and exploitable ferrocene CV signal for sensing purposes. • Sensitive enzymeless detection of hydrogen peroxide at low potentials. • Enzymatic Sensitive detection of glucose on GOx-modified graphene electrode.

  9. Ferrocene-functionalized graphene electrode for biosensing applications

    International Nuclear Information System (INIS)

    Rabti, Amal; Mayorga-Martinez, Carmen C.; Baptista-Pires, Luis; Raouafi, Noureddine; Merkoçi, Arben

    2016-01-01

    A novel ferrocene-functionalized reduced graphene oxide (rGO)-based electrode is proposed. It was fabricated by the drop casting of ferrocene-functionalized graphene onto polyester substrate as the working electrode integrated within screen-printed reference and counter electrodes. The ferrocene-functionalized rGO has been fully characterized using FTIR, XPS, contact angle measurements, SEM and TEM microscopy, and cyclic voltammetry. The XPS and EDX analysis showed the presence of Fe element related to the introduced ferrocene groups, which is confirmed by a clear CV signal at ca. 0.25 V vs. Ag/AgCl (0.1 KCl). Mediated redox catalysis of H_2O_2 and bio-functionalization with glucose oxidase for glucose detection were achieved by the bioelectrode providing a proof for potential biosensing applications. - Graphical abstract: An easy-to-prepare standalone graphene electrode was obtained by the drop-casting ferrocene-functionalized rGO on PET polymer. This electrode can be used as an enzymeless electrochemical sensor for the detection of hydrogen peroxide or as an amperometric enzyme-based biosensor for sensitive glucose detection. - Highlights: • A novel ferrocene-functionalized reduced graphene oxide based electrode. • Ease of preparation by drop-casting of Fc-modified graphene and chitosan mixture. • Well-defined and exploitable ferrocene CV signal for sensing purposes. • Sensitive enzymeless detection of hydrogen peroxide at low potentials. • Enzymatic Sensitive detection of glucose on GOx-modified graphene electrode.

  10. The synthesis of nucleoside bases with 14 C

    International Nuclear Information System (INIS)

    Matloubi, H.; Mehrdad, M.

    1997-01-01

    Labelled organic compounds have been widely and diligently applied to research problems in life science and chemistry. In many laboratories they have lost their novelty and have been become conventional research tools since long time ago. these applications frequently require organic compounds substituted (or labelled) with isotopes, but the isotopes are (with certain exception) extracted in first place in simple inorganic forms. The conversion of these simple form into the more or less complex labelled compounds called for by research workers has become in effect a new branch of practical organic chemistry. The preparation of labelled compounds, carbon-14 is probably more extensively and variously used than any other isotope. It emits only beta-particles. In this project, two kinds of nucleoside bases under the name uracil-2- 14 C and thymine (methyl- 14 C) were prepared.(author). 14 refs., 3 figs., 2 tabs

  11. Vapour pressures and enthalpies of vaporization of a series of the ferrocene derivatives

    International Nuclear Information System (INIS)

    Emel'yanenko, Vladimir N.; Verevkin, Sergey P.; Krol, Olesya V.; Varushchenko, Raisa M.; Chelovskaya, Nelly V.

    2007-01-01

    Vapour pressures of the ferrocene, ferrocene-methanol, benzyl-ferrocene, and benzoyl-ferrocene have been determined by the transpiration method. The molar enthalpies of sublimation Δ cr g H m and of vaporization Δ l g H m have been determined from the temperature dependence of the vapour pressure. The molar enthalpies of fusion of these compounds were measured by d.s.c. The measured data sets of vaporization, sublimation, and fusion enthalpies were checked for internal consistency

  12. Nucleoside analog toxicity and nucleoside kinase deficiency : Effects on mitochondrial DNA

    OpenAIRE

    Bjerke, Mia

    2008-01-01

    Nucleoside analogs are modified nucleosides used in treatment of cancer and viral infections. They are dependent on intracellular phosphorylation to be pharmacologically active. Deoxyribonucleoside kinases catalyze the rate-limiting step in the phosphorylation of many clinically used nucleoside analogs. Human cells contain four distinct deoxyribonucleoside kinases that have partially overlapping substrate specificities for both naturally occurring deoxyribonucleosides as wel...

  13. Marine Nucleosides: Structure, Bioactivity, Synthesis and Biosynthesis

    Directory of Open Access Journals (Sweden)

    Ri-Ming Huang

    2014-12-01

    Full Text Available Nucleosides are glycosylamines that structurally form part of nucleotide molecules, the building block of DNA and RNA. Both nucleosides and nucleotides are vital components of all living cells and involved in several key biological processes. Some of these nucleosides have been obtained from a variety of marine resources. Because of the biological importance of these compounds, this review covers 68 marine originated nucleosides and their synthetic analogs published up to June 2014. The review will focus on the structures, bioactivities, synthesis and biosynthetic processes of these compounds.

  14. Covalent modification and exfoliation of graphene oxide using ferrocene

    Science.gov (United States)

    Avinash, M. B.; Subrahmanyam, K. S.; Sundarayya, Y.; Govindaraju, T.

    2010-09-01

    Large scale preparation of single-layer graphene and graphene oxide is of great importance due to their potential applications. We report a simple room temperature method for the exfoliation of graphene oxide using covalent modification of graphene oxide with ferrocene to obtain single-layer graphene oxide sheets. The samples were characterized by FESEM, HRTEM, AFM, EDAX, FT-IR, Raman and Mössbauer spectroscopic studies. HRTEM micrograph of the covalently modified graphene oxide showed increased interlayer spacing of ~2.4 nm due to ferrocene intercalation. The presence of single-layer graphene oxide sheets were confirmed by AFM studies. The covalently modified ferrocene-graphene oxide composite showed interesting magnetic behavior.Large scale preparation of single-layer graphene and graphene oxide is of great importance due to their potential applications. We report a simple room temperature method for the exfoliation of graphene oxide using covalent modification of graphene oxide with ferrocene to obtain single-layer graphene oxide sheets. The samples were characterized by FESEM, HRTEM, AFM, EDAX, FT-IR, Raman and Mössbauer spectroscopic studies. HRTEM micrograph of the covalently modified graphene oxide showed increased interlayer spacing of ~2.4 nm due to ferrocene intercalation. The presence of single-layer graphene oxide sheets were confirmed by AFM studies. The covalently modified ferrocene-graphene oxide composite showed interesting magnetic behavior. Electronic supplementary information (ESI) available: Magnetic data; AFM images; TEM micrographs; and Mössbauer spectroscopic data. See DOI: 10.1039/c0nr00024h

  15. Pd0-Catalyzed Methyl Transfer on Nucleosides and Oligonucleotides, Envisaged as a PET Tracer

    Directory of Open Access Journals (Sweden)

    Eric Fouquet

    2013-11-01

    Full Text Available The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under “ligandless” conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute conditions, thus affording a rapid and efficient new method for oligonucleotide labelling with carbon-11.

  16. 1-(Ferrocen-1-ylmethyl-3-methylimidazol-3-ium iodide

    Directory of Open Access Journals (Sweden)

    Vincent O. Nyamori

    2012-12-01

    Full Text Available The structure of the title compound, [Fe(C5H5(C10H12N2]I, consists of a 1-(ferrocen-1-ylmethyl-3-methylimidazolium cation which is counter-balanced by an iodide anion. The cyclopentadienyl (Cp rings of the ferrocene unit have a slightly staggered conformation skewed from an ideal eclipsed conformation by an angle of 3.5 (6°. The interplanar angle between the Cp and the imidazole ring is 67.94 (2°.

  17. Pentose phosphates in nucleoside interconversion and catabolism.

    Science.gov (United States)

    Tozzi, Maria G; Camici, Marcella; Mascia, Laura; Sgarrella, Francesco; Ipata, Piero L

    2006-03-01

    Ribose phosphates are either synthesized through the oxidative branch of the pentose phosphate pathway, or are supplied by nucleoside phosphorylases. The two main pentose phosphates, ribose-5-phosphate and ribose-1-phosphate, are readily interconverted by the action of phosphopentomutase. Ribose-5-phosphate is the direct precursor of 5-phosphoribosyl-1-pyrophosphate, for both de novo and 'salvage' synthesis of nucleotides. Phosphorolysis of deoxyribonucleosides is the main source of deoxyribose phosphates, which are interconvertible, through the action of phosphopentomutase. The pentose moiety of all nucleosides can serve as a carbon and energy source. During the past decade, extensive advances have been made in elucidating the pathways by which the pentose phosphates, arising from nucleoside phosphorolysis, are either recycled, without opening of their furanosidic ring, or catabolized as a carbon and energy source. We review herein the experimental knowledge on the molecular mechanisms by which (a) ribose-1-phosphate, produced by purine nucleoside phosphorylase acting catabolically, is either anabolized for pyrimidine salvage and 5-fluorouracil activation, with uridine phosphorylase acting anabolically, or recycled for nucleoside and base interconversion; (b) the nucleosides can be regarded, both in bacteria and in eukaryotic cells, as carriers of sugars, that are made available though the action of nucleoside phosphorylases. In bacteria, catabolism of nucleosides, when suitable carbon and energy sources are not available, is accomplished by a battery of nucleoside transporters and of inducible catabolic enzymes for purine and pyrimidine nucleosides and for pentose phosphates. In eukaryotic cells, the modulation of pentose phosphate production by nucleoside catabolism seems to be affected by developmental and physiological factors on enzyme levels.

  18. Charge-transfer spectra of ferrocene in halocarbon solvents under ...

    Indian Academy of Sciences (India)

    Unknown

    Ferrocene (bis(cyclopentadienyl) iron: (C5H5)2Fe; abbreviated as FcH, the first ... For removing the dissolved oxygen from the solution, dry nitrogen gas was allowed to ... The error limit involved in the excitation wavelength is ~ 0⋅2 nm and the.

  19. Smoke reduction from pool fires using ferrocene and derivatives

    International Nuclear Information System (INIS)

    Mitchell, J.B.A.; Moir, M.E.

    1992-01-01

    A series of acyl and alkyl substituted ferrocene derivatives were tested as smoke control agents in laboratory-scale burn tests. In the tests, the soot produced by a given volume was collected on a filter and its weight measured to determine the relative smoke reducing effectiveness of the various derivatives. As the molecular weight of the derivative increases, the effectiveness decreases when added at a fixed weight concentration. The heavier derivatives were much less effective on a per-weight basis than ferrocene, while the multiply substituted compounds appeared to be more effective. In field tests conducted to evaluate the effectiveness of ferrocene in reducing smoke during combustion of other hydrocarbon fuels, it was found that there was a very large soot yield from gasoline fuel, higher than for crude oil even when ferrocene was used. In meso-scale tests, a drastic reduction in smoke yield was obtained when using a new liquid smoke-control additive during combustion of dilbit (bitumen diluted by gas condensate) floating on water. 3 refs., 5 figs., 1 tab

  20. Recommended vapor pressure and thermophysical data for ferrocene

    Czech Academy of Sciences Publication Activity Database

    Fulem, Michal; Růžička, K.; Červinka, C.; Rocha, M.A.A.; Santos, L.M.N.B.F.; Berg, R.F.

    2013-01-01

    Roč. 57, FEB (2013), 530-540 ISSN 0021-9614 Institutional support: RVO:68378271 Keywords : ferrocene * vapor pressure * heat capacity * ideal gas thermodynamic properties * sublimation enthalpy * recommended vapor pressure equation Subject RIV: BJ - Thermodynamics Impact factor: 2.423, year: 2013

  1. Solubilities of ferrocene and acetylferrocene in supercritical carbon dioxide

    DEFF Research Database (Denmark)

    Kazemi, Somayeh; Belandria, Veronica; Janssen, Nico

    2012-01-01

    In this work, the solubilities of ferrocene and acetylferrocene in supercritical carbon dioxide (scCO2) were measured using an analytical method in a quasi-flow apparatus. High-performance liquid chromatography was applied through an online sampling procedure to determine the concentration...

  2. Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.

    Science.gov (United States)

    Boyd, Mark A; Amin, Janaki; Mallon, Patrick W G; Kumarasamy, Nagalingeswaran; Lombaard, Johan; Wood, Robin; Chetchotisakd, Ploenchan; Phanuphak, Praphan; Mohapi, Lerato; Azwa, Iskandar; Belloso, Waldo H; Molina, Jean-Michel; Hoy, Jennifer; Moore, Cecilia L; Emery, Sean; Cooper, David A

    2017-01-01

    Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N

  3. Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

    Science.gov (United States)

    Niu, Guoqing; Tan, Huarong

    2015-02-01

    The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics. Copyright © 2014. Published by Elsevier Ltd.

  4. Synthesis and application of a triazene-ferrocene modifier for immobilization and characterization of oligonucleotides at electrodes.

    Science.gov (United States)

    Hansen, Majken N; Farjami, Elaheh; Kristiansen, Martin; Clima, Lilia; Pedersen, Steen Uttrup; Daasbjerg, Kim; Ferapontova, Elena E; Gothelf, Kurt V

    2010-04-16

    A new DNA modifier containing triazene, ferrocene, and activated ester functionalities was synthesized and applied for electrochemical grafting and characterization of DNA at glassy carbon (GC) and gold electrodes. The modifier was synthesized from ferrocenecarboxylic acid by attaching a phenyltriazene derivative to one of the ferrocene Cp rings, while the other Cp ring containing the carboxylic acid was converted to an activated ester. The modifier was conjugated to an amine-modified DNA sequence. For immobilization of the conjugate at Au or GC electrodes, the triazene was activated by dimethyl sulfate for release of the diazonium salt. The salt was reductively converted to the aryl radical which was readily immobilized at the surface. DNA grafted onto electrodes exhibited remarkable hybridization properties, as detected through a reversible shift in the redox potential of the Fc redox label upon repeated hybridization/denaturation procedures with a complementary target DNA sequence. By using a methylene blue (MB) labeled target DNA sequence the hybridization could also be followed through the MB redox potential. Electrochemical studies demonstrated that grafting through the triazene modifier can successfully compete with existing protocols for DNA immobilization through the commonly used alkanethiol linkers and diazonium salts. Furthermore, the triazene modifier provides a practical one-step immobilization procedure.

  5. Solubility of solid ferrocene in pressurized hot water

    Czech Academy of Sciences Publication Activity Database

    Karásek, Pavel; Hohnová, Barbora; Planeta, Josef; Roth, Michal

    2010-01-01

    Roč. 55, č. 8 (2010), s. 2866-2869 ISSN 0021-9568 R&D Projects: GA ČR GA203/07/0886; GA ČR GA203/08/1465; GA ČR GA203/08/1536 Institutional research plan: CEZ:AV0Z40310501 Keywords : pressurized hot water * ferrocene * solubility Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.089, year: 2010

  6. Synthesis, characterization and catalytic utilization of a ferrocene diamidodiphosphane

    Czech Academy of Sciences Publication Activity Database

    Štěpnička, P.; Schulz, J.; Císařová, I.; Fejfarová, Karla

    2007-01-01

    Roč. 72, č. 4 (2007), s. 453-467 ISSN 0010-0765 Grant - others:GAMŠk(CZ) LC06070 Program:LC Institutional research plan: CEZ:AV0Z10100521 Keywords : ferrocene * phosphines * amides * Suzuki-Miyaura cross-coupling, crystal structure determination * igands * x-ray diffraction Subject RIV: CA - Inorganic Chemistry Impact factor: 0.879, year: 2007

  7. Effects of tritium-labeled pyrimidine nucleosides on epithelial cell proliferation in the mouse. I. Cytodynamic perturbations in normal circadian rhythms after a single injection of 3H-thymidine

    International Nuclear Information System (INIS)

    Olsson, L.

    1976-01-01

    In a combined stathmokinetic, autoradiographic, and microspectrophotometric study on the cytodynamics in mouse epidermis, cirdardian rhythms were observed in the number of cells within the various phases (except G 2 ) of the mitotic cell cycle, and in mitotic rate. S-Phase influx and efflux were computed and were found to vary during a 24-hr period. No diurnal rhythm was observed in mitotic rate in the epithelium of small intestine. 3 H-Thymidine (1 μCi/g; sp act 5 Ci/mmol) induced mitotic delay in labeled cells 2 to 8 hr after administration. A supranormal mitotic activity in unlabeled cells was observed 12 to 24 hr after injection of 3 H-TdR. ''Cold'' thymidine had no effects on epidermal cell proliferation. S-Phase duration and average cell cycle time were estimated by traditional cell kinetic methods. The results suggest a 3 H-TdR-induced synchrony in cells entering the S phase 0 to 15 hr after injection of the precursor. A mitotic delay was seen in small intestinal epithelium 2 to 6 hr after injection of the precursor

  8. Aptasensor for ATP based on analyte-induced dissociation of ferrocene-aptamer conjugates from manganese dioxide nanosheets on a screen-printed carbon electrode

    International Nuclear Information System (INIS)

    Tang, Dianping; Hou, Li

    2016-01-01

    The authors report on a new electrochemical aptasensing strategy for the determination of adenosine - 5’-triphosphate (ATP) at picomolar levels. First, manganese dioxide (MnO 2 ) nanosheets with an average size of ∼70 nm were synthesized via a hot-injection method on the basis of reaction between potassium permanganate and the cationic detergent cetyltrimethylammonium bromide. The resulting MnO 2 nanosheets were then immobilized onto a pretreated screen-printed carbon electrode which readily binds the ferrocene-labeled ATP aptamer through the van der Waals force between the nucleobases and the basal plane of the nanoflakes. The immobilized ferrocene-aptamer conjugates activates the electrical contact with the electrode and produces a strong signal in the potentials scanned (0.0 to 1.0 V vs. Ag/AgCl). Upon addition of ATP, it will react with the aptamer and cause the dissociation of the ferrocene-aptamer from the nanosheets, this resulting in a decrease in the electrical signal. Under optimal conditions, this platform exhibits a detection limit as low as 0.32 nM of ATP. The repeatability and intermediate precision is below 10.7 % at a 10 nM concentration level. The method was applied to analyze blank fetal calf serum spiked with ATP, and the recoveries (at 3 concentration levels) ranged between 91.3 and 118 %. This detection scheme is rapid, simple, cost-effective, and does not require extensive sample preparation or multiple washing steps. (author)

  9. Rh(III-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

    Directory of Open Access Journals (Sweden)

    Satoshi Takebayashi

    2012-10-01

    Full Text Available [RhCp*(OAc2(H2O] [Cp* = pentamethylcyclopentadienyl] catalyzed the C–H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF4·OEt2. A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities.

  10. Genetics Home Reference: purine nucleoside phosphorylase deficiency

    Science.gov (United States)

    ... the expand/collapse boxes. Description Purine nucleoside phosphorylase deficiency is one of several disorders that damage the immune system and cause severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from foreign invaders such as bacteria, viruses, and ...

  11. A temperature induced ferrocene–ferrocenium interconversion in a ferrocene functionalized μ3-O chromium carboxylate

    International Nuclear Information System (INIS)

    Mereacre, Valeriu; Schlageter, Martin; Powell, Annie K.

    2015-01-01

    The infrared spectra and 57 Fe Mössbauer measurements of a ferrocenecarboxylate functionalized {Cr 3 O} complex in solid state are reported. It was established that conjugation of ferrocene Cp orbitals with the π orbitals of the adjacent carboxylic group stabilizes the trapped mixed-valence state leading to an intriguing coexistence of ferrocene and ferrocenium species giving rise to a new type of compound showing valence tautomerism in the solid state. - Highlights: • A stabilized ferrocene trapped mixed-valence state is reported. • New type of compound showing valence tautomerism in solid state. • A thermally induced electron transfer and a mixed-valence state near room temperature

  12. Tropanol esters of metallocene carboxylic acids. Syntheses, labelling with 103Ru and sup(103m)Rh and organ distribution

    International Nuclear Information System (INIS)

    Wenzel, M.; Wu, Y.

    1988-01-01

    The tropanol esters of the carboxylic acids of ferrocene, 103 Ru-ruthenocene and sup(103m)Rh-rhodocinium were synthezised. The organ distribution of the 103 Ru or sup(103m)Rh labelled tropanol-esters were investigated. Only the 103 Ru labelled ester showed a high heart/blood ratio. (author)

  13. Redox-Enabled, pH-Disabled Pyrazoline-Ferrocene INHIBIT Logic Gates.

    Science.gov (United States)

    Scerri, Glenn J; Cini, Miriam; Schembri, Jonathan S; da Costa, Paola F; Johnson, Alex D; Magri, David C

    2017-07-05

    Pyrazoline-ferrocene conjugates with an "electron-donor-spacer-fluorophore-receptor" format are demonstrated as redox-fluorescent two-input INHIBIT logic gates. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Electrochromic Behaviors of Water-Soluble Polyaniline with Covalently Bonded Acetyl Ferrocene

    Science.gov (United States)

    Xiong, Shanxin; Wang, Ru; Li, Shuaishuai; Wu, Bohua; Chu, Jia; Wang, Xiaoqin; Zhang, Runlan; Gong, Ming

    2018-04-01

    A novel ferrocene-containing hybrid electrochromic material was synthesized via copolymerization of aniline with p-phenylenediamine functionalized acetyl ferrocene in the presence of poly (styrene sulfonate) dopant in an aqueous medium, and neat polyaniline (PANI) was prepared for comparison. The polymerization characteristics and the structure of the copolymer were systematically studied by Fourier-transform infrared, meanwhile, their electrochromic properties and electrochemical behaviors were tested by UV-vis spectra, cyclic voltammetry and electrochemical impedance spectroscopy (EIS). It was found that the strong covalent bond and large conjugated system between PANI and ferrocene enhance the electron transfer rate and electron delocalization in the ferrocene-polyaniline (Fc-PANI) hybrid. In particular, the electrochromic device with Fc-PANI as the active layer shows significant enhancement in optical contrast over the PANI-based device.

  15. Heterogeneous electron transfer kinetics and electrocatalytic behaviour of mixed self-assembled ferrocenes and SWCNT layers

    CSIR Research Space (South Africa)

    Nkosi, D

    2010-01-01

    Full Text Available The electron transfer dynamics and electrocatalytic behaviour of ferrocene-terminated self-assembled monolayers (SAMs), co-adsorbed with single-walled carbon nanotubes (SWCNTs) on a gold electrode, have been interrogated for the first time...

  16. Positron annihilation studies on reactor irradiated and thermal annealed ferrocene

    International Nuclear Information System (INIS)

    Marques Netto, A.; Carvalho, R.S.; Magalhaes, W.F.; Sinisterra, R.D.

    1996-01-01

    Retention and thermal annealing following (n, γ) reaction in solid ferrocene, Fe(C 5 H 5 ) 2 , were studied by positron annihilation lifetime spectroscopy (PAL). Positronium (Ps) formation was observed in the non-irradiated compound with a probability or intensity (I 3 ) of 30%. Upon irradiation of the compound with thermal neutrons in a nuclear reactor, I 3 decreases with increasing irradiation time. Thermal treatment again increases I 3 values from 16% to 25%, revealing an important proportion of molecular reformation without variation of the ortho-positronium lifetime (τ 3 ). These results point out the major influence of the electronic structure as determining the Ps yields in the pure complex. In the irradiated and non irradiated complexes the results are satisfactorily explained on the basis of the spur model. (orig.)

  17. Tetrofuranose nucleoside phosphonic acids: Synthesis and properties

    Czech Academy of Sciences Publication Activity Database

    Poláková, Ivana; Buděšínský, Miloš; Točík, Zdeněk; Rosenberg, Ivan

    2011-01-01

    Roč. 76, č. 5 (2011), s. 503-536 ISSN 0010-0765 R&D Projects: GA AV ČR KAN200520801; GA ČR GA203/09/0820; GA MŠk(CZ) LC06061; GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : tetrofuranosyl phosphonate * nucleotide analogues * phosphonomethoxy nucleosides * sugar hydroxyphosphonates Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  18. Protein labelling with stable isotopes: strategies

    International Nuclear Information System (INIS)

    Lirsac, P.N.; Gilles, N.; Jamin, N.; Toma, F.; Gabrielsen, O.; Boulain, J.C.; Menez, A.

    1994-01-01

    A protein labelling technique with stable isotopes has been developed at the CEA: a labelled complete medium has been developed, performing as well as the Luria medium, but differing from it because it contains not only free aminated acids and peptides, but also sugars (96% of D-glucopyrannose) and labelled nucleosides. These precursors are produced from a labelled photosynthetic micro-organisms biomass, obtained with micro-algae having incorporated carbon 13, nitrogen 15 and deuterium during their culture. Labelling costs are reduced. 1 fig., 1 tab., 3 refs

  19. Synthesis and Characterization of Ferrocene Derivatives and Preliminarily Electrocatalytic Oxidation of L-Cysteine at Nafion-Ferrocene Derivatives Modified Glassy Carbon Electrode

    Directory of Open Access Journals (Sweden)

    Jianping Yong

    2014-01-01

    Full Text Available Five new structural ferrocene derivatives (2a~2e were firstly synthesized and characterized by 1H NMR, 13C NMR, ESI-MS, and XRD. Subsequently, the preliminarily electrocatalytic oxidation of L-cysteine (L-Cys at nafion-ferrocene derivatives modified glassy carbon electrode (GCE has also been investigated by cyclic voltammetry. The results showed that 2e can dramatically electrocatalyze the oxidation of L-cysteine at its modified GCE in 0.1 mol L−1 NaNO3 aqueous solution with a quasireversible process with ΔEp≈55 mV.

  20. A conformationally locked tricyclic nucleoside. Synthesis, crystal structure and incorporation into oligonucleotides

    DEFF Research Database (Denmark)

    Ravn, Jacob; Thorup, Niels; Nielsen, Poul

    2001-01-01

    A tricyclic nucleoside is synthesised from a bicyclic nucleoside precursor by applying a stereoselective dihydroxylation, a regioselective tosylation and an intramolecular ether formation. This tricyclic nucleoside is constructed as a conformationally locked thymidine analogue and has been analys...

  1. Micro-sized organometallic compound of ferrocene as high-performance anode material for advanced lithium-ion batteries

    Science.gov (United States)

    Liu, Zhen; Feng, Li; Su, Xiaoru; Qin, Chenyang; Zhao, Kun; Hu, Fang; Zhou, Mingjiong; Xia, Yongyao

    2018-01-01

    An organometallic compound of ferrocene is first investigated as a promising anode for lithium-ion batteries. The electrochemical properties of ferrocene are conducted by galvanostatic charge and discharge. The ferrocene anode exhibits a high reversible capacity and great cycling stability, as well as superior rate capability. The electrochemical reaction of ferrocene is semi-reversible and some metallic Fe remains in the electrode even after delithiation. The metallic Fe formed in electrode and the stable solid electrolyte interphase should be responsible for its excellent electrochemical performance.

  2. Differential Labeling of Free and Disulfide-Bound Thiol Functions in Proteins

    NARCIS (Netherlands)

    Seiwert, B.; Hayen, H.; Karst, U.

    2008-01-01

    A method for the simultaneous determination of the number of free cysteine groups and disulfide-bound cysteine groups in proteins has been developed based on the sequential labeling of free and bound thiol functionalities with two ferrocene-based maleimide reagents. Liquid

  3. Desulfurization of 2-thiouracil nucleosides: conformational studies of 4-pyrimidinone nucleosides.

    Science.gov (United States)

    Kraszewska, Karina; Kaczyńska, Iwona; Jankowski, Stefan; Karolak-Wojciechowska, Janina; Sochacka, Elzbieta

    2011-04-01

    4-Pyrimidinone ribofuranoside (H(2)o(4)U) and 4-pyrimidinone 2'-deoxyribofuranoside (dH(2)o(4)U) were synthesized by the oxidative desulfurization of parent 2-thiouracil nucleosides with m-chloroperbenzoic acid. The crystal structures of H(2)o(4)U and dH(2)o(4)U and their conformations in solution were determined and compared with corresponding 2-thiouracil and uracil nucleosides. The absence of a large 2-thiocarbonyl/2-carbonyl group in the nucleobase moiety results in C2'-endo puckering of the ribofuranose ring (S conformer) in the crystal structure of H(2)o(4)U, which is not typical of RNA nucleosides. Interestingly, the hydrogen bonding network in the crystals of dH(2)o(4)U stabilizes the sugar moiety conformation in the C3'-endo form (N conformer), rarely found in DNA nucleosides. In aqueous solution, dH(2)o(4)U reveals a similar population of the C2'-endo conformation (65%) to that of 2'-deoxy-2-thiouridine (62%), while the 62% population of the S conformer for H(2)o(4)U is significantly different from that of the parent 2-thiouridine, for which the N conformer is dominant (71%). Such a difference may be of biological importance, as the desulfurization process of natural tRNA 2-thiouridines may occur under conditions of oxidative stress in the cell and may influence the decoding process. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. A monoclonal antibody that specifically recognizes m6A nucleoside

    OpenAIRE

    Espuny, Ruth; Castro, Ana; Codony, Carles; Eritja Casadellà, Ramón; Bach-Elias, Montse

    1998-01-01

    A hybridoma against the nucleoside m6A has been obtained from mouse spleen. This hybridoma was named H65 and it secretes monoclonal antibodies anti-m6A. The competition assays showed that the monoclonal antibody was highly specific for m6A nucleoside.

  5. Two nucleoside transporters in Lactococcus lactis with different substrate specificities

    DEFF Research Database (Denmark)

    Martinussen, Jan; Sørensen, Claus; Jendresen, Christian Bille

    2010-01-01

    , and the utilization of nucleotides is dependent on exogenous phosphatases. The composition of transporters with specificity for purine and pyrimidine nucleosides and nucleobases is subject to variation. The ability of Lactococcus lactis to transport different nucleosides across the cell membrane was characterized...

  6. Synthesis, antioxidant and antibacterial activities of 3-nitrophenyl ferrocene

    Science.gov (United States)

    Benabdesselam, S.; Izza, H.; Lanez, T.; Guechi, E. K.

    2018-03-01

    The current work aims in its first part to synthesize 3-nitrophenylferrocene after diazotizing nitroaniline in the meta position by the sodium nitrite and the formation of the corresponding diazonium salt: 3-nitrobenzendiazonium sulfate, then the salt in solution was added to the ferrocene for the purpose of introducing the nitrophenyl moiety thereon (arylation) and the formation of 3-nitrophenylferrocene. The second part is devoted to the study of the antioxidant activity of 3-NPF by applying the trapping test of superoxide radical using cyclic voltammetry, the free radical DPPH trapping test by spectrophotometry. The results showed that 3-nitrophenylferrocene has a scavenging effect of DPPH radical with IC50 = 1.44mg/ml, superoxide radical with IC50=5.38mg/ml. The third part is devoted to the study of antibacterial activity of the synthesized compound tested on four strains of bacteria: Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Klebsiella pneumoniae. The obtained results clearly showed that 3-nitrophenylferrocene has low activities on the four bacterial strains with diameters of inhibition zones do not exceeding 17 mm at concentrations of 25mg/ml.

  7. Construction of ferrocene modified conducting polymer based amperometric urea biosensor.

    Science.gov (United States)

    Dervisevic, Muamer; Dervisevic, Esma; Senel, Mehmet; Cevik, Emre; Yildiz, Huseyin Bekir; Camurlu, Pınar

    2017-07-01

    Herein, an electrochemical urea sensing bio-electrode is reported that has been constructed by firstly electropolymerizing 4-(2,5-Di(thiophen-2-yl)-1H-pyrrol-1-yl)aniline monomer (SNS-Aniline) on Pencil Graphite Electrode (PGE), then modifying the polymer coated electrode surface with di-amino-Ferrocene (DAFc) as the mediator, and lastly Urease enzyme through glutaraldehyde crosslinking. The effect of pH, temperature, polymer thickness, and applied potential on the electrode current response was investigated besides performing storage and operational stability experiments with the interference studies. The resulting urea biosensor's amperometric response was linear in the range of 0.1-8.5mM with the sensitivity of 0.54μA/mM, detection limit of 12μM, and short response time of 2s. The designed bio-electrode was tested with real human blood and urine samples where it showed excellent analytical performance with insignificant interference. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Modification of Au surfaces using new ferrocene derivatives

    International Nuclear Information System (INIS)

    Diaz-Ortiz, Tanya L.; Malave-Leon, Maria; Rivera-Claudio, Mirna; Castillo-Ramirez, Jorge; Cabrera-Martinez, Carlos R.; Brito-Gomez, Rosa; Tremont, Rolando J.

    2008-01-01

    Gold surfaces have been modified by self-assembled techniques. Here the adsorption time of diasteroisomers (1R, 3S)-1-ferrocenyl-3-methyl-4,4-diphenyl-2,5-dioxacyclopentane and (1S, 3S)-1-ferrocenyl-3-methyl-4,4-diphenyl-2,5-dioxacyclopentane (, 3a and 3b) at a Au surface in ethanol solution was controlled. This study was followed by electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) analysis. The method used for the surface modification was the control of exposure time of a Au surface in the modifier/ethanol solution. It was demonstrated by EIS and XPS that the Au surface was modified with mixture of compounds 3a + 3b, avoiding the electron transference in the interface. It was also observed that the organometallic molecule indeed had been adsorbed on the Au surface. In addition, evidence seems to conclude that the molecule-Au interaction is through the electrons of cyclopentadienyl moiety, where the oxygen atoms are near the air-molecule interface and the iron atom is near the Au surface. This type of interaction of the ferrocene derivatives with gold surfaces has not been reported by any other author

  9. Ferrocene: Disposition following nose-only inhalation by the rat

    International Nuclear Information System (INIS)

    Slauter, R.W.; Tippin, T.K.; Jeffcoat, A.R.; Matthews, H.B.

    1990-01-01

    Ferrocene (FCN) is a volatile solid organometallic proposed for use as an anti-knock additive in gasoline. Such use would provide significant potential for human exposure via inhalation. Nose-only exposure of male F344 rats over 6 h to constant concentrations of 5 and 25 ng of [ 14 C]FCN/mL air was conducted by blending correct proportions of an air stream concentrated with [ 14 C]FCN vapor with one that was FCN free. Fractional pulmonary absorption of FCN was estimated to be ca. 66 and 55% with concentrations of 14 C in blood increasing steadily throughout the exposure period to 80 and 370 ng-eq of FCN/mL, respectively. Disappearance of 14 C from the blood was multiphasic (terminal t 1/2 =∼2 d) following inhalation exposure, resulting in blood concentrations of 10 and 50 ng-eq of FCN/mL 72 h after end of exposure. More than 80% of the recovered 14 C was in the 0-72 h urine, approximately half of which was a single metabolite (radio-HPLC). Unchanged FCN was excreted in only minor amounts ( 14 C were also excreted in feces (ca. 10% of total) and breath (ca. 4% of total). Neither lung nor nasopharynx had tissue to blood ratios of 14 C>3 72 h after exposure. Similar disposition was shown after an iv bolus of 1.0 mg of [ 14 C]FCN/kg body weight

  10. Dual door entry to exciplex emission in a chimeric DNA duplex containing non-nucleoside-nucleoside pair.

    Science.gov (United States)

    Bag, Subhendu Sekhar; Talukdar, Sangita; Kundu, Rajen; Saito, Isao; Jana, Subhashis

    2014-01-25

    Dual door entry to exciplex formation was established in a chimeric DNA duplex wherein a fluorescent non-nucleosidic base surrogate () is paired against a fluorescent nucleosidic base surrogate (). Packing of the nucleobases via intercalative stacking interactions led to an exciplex emission either via FRET from the donor or direct excitation of the FRET acceptor .

  11. Linkage of α-cyclodextrin-terminated poly(dimethylsiloxanes by inclusion of quasi bifunctional ferrocene

    Directory of Open Access Journals (Sweden)

    Helmut Ritter

    2013-07-01

    Full Text Available We report the noncovalent linkage of terminally substituted oligo(dimethylsiloxanes bearing α-cyclodextrins (α-CD as host end groups for the cyclopentadienyl rings of ferrocene. This double complexation of unsubstituted ferrocene leads to a supramolecuar formation of the siloxane strands. Structural characterization was performed by the use of 1H NMR and IR spectroscopy and by mass spectrometry. Electron microscopy studies and dynamic light scattering measurements show a significant decrease of the derivative size after the complexation with ferrocene. In addition, further evidence for the successful complexation of the end groups was verified by the shifts of the protons in the 1H NMR spectra and in the correlation signals of the 2D ROESY NMR spectra.

  12. Liquid- and Gas-Phase Diffusion of Ferrocene in Thin Films of Metal-Organic Frameworks

    Directory of Open Access Journals (Sweden)

    Wencai Zhou

    2015-06-01

    Full Text Available The mass transfer of the guest molecules in nanoporous host materials, in particular in metal-organic frameworks (MOFs, is among the crucial features of their applications. By using thin surface-mounted MOF films in combination with a quartz crystal microbalance (QCM, the diffusion of ferrocene vapor and of ethanolic and hexanic ferrocene solution in HKUST-1 was investigated. For the first time, liquid- and gas-phase diffusion in MOFs was compared directly in the identical sample. The diffusion coefficients are in the same order of magnitude (~10−16 m2·s−1, whereas the diffusion coefficient of ferrocene in the empty framework is roughly 3-times smaller than in the MOF which is filled with ethanol or n-hexane.

  13. Liquid- and Gas-Phase Diffusion of Ferrocene in Thin Films of Metal-Organic Frameworks

    Science.gov (United States)

    Zhou, Wencai; Wöll, Christof; Heinke, Lars

    2015-01-01

    The mass transfer of the guest molecules in nanoporous host materials, in particular in metal-organic frameworks (MOFs), is among the crucial features of their applications. By using thin surface-mounted MOF films in combination with a quartz crystal microbalance (QCM), the diffusion of ferrocene vapor and of ethanolic and hexanic ferrocene solution in HKUST-1 was investigated. For the first time, liquid- and gas-phase diffusion in MOFs was compared directly in the identical sample. The diffusion coefficients are in the same order of magnitude (~10−16 m2·s−1), whereas the diffusion coefficient of ferrocene in the empty framework is roughly 3-times smaller than in the MOF which is filled with ethanol or n-hexane.

  14. An Efficient and Facile Methodology for Bromination of Pyrimidine and Purine Nucleosides with Sodium Monobromoisocyanurate (SMBI

    Directory of Open Access Journals (Sweden)

    Roger Stromberg

    2013-10-01

    Full Text Available An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI. Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.

  15. Carbohydrates/nucleosides/RNA-DNA-ligand interactions

    International Nuclear Information System (INIS)

    Kaptein, R.; McConnell, B.; Serianni, A.S.; Silks, L.A. III.

    1994-01-01

    Carbohydrate and nucleotide structural determination using modern spectroscopic techniques is dependent on our ability to label oligonucleotides and oligosaccharides with stable isotopes. Uniform Carbon 13 and Nitrogen 15 labeling of oligonucleotides is important to present-day efforts, which are focused on determining the structure of relatively small oligosaccharides and oligonucleotides, which form the elements of larger structures. Because of the relatively recent interest in three-dimensional structure, the development of techniques used to label them has lagged behind parallel techniques used to label peptides and proteins. Therefore, this group's discussion focused primarily on problems faced today in obtaining oligonucleotides labeled uniformly with carbon 13 and nitrogen 15

  16. Carbohydrates/nucleosides/RNA-DNA-ligand interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kaptein, R.; McConnell, B.; Serianni, A.S.; Silks, L.A. III

    1994-12-01

    Carbohydrate and nucleotide structural determination using modern spectroscopic techniques is dependent on our ability to label oligonucleotides and oligosaccharides with stable isotopes. Uniform Carbon 13 and Nitrogen 15 labeling of oligonucleotides is important to present-day efforts, which are focused on determining the structure of relatively small oligosaccharides and oligonucleotides, which form the elements of larger structures. Because of the relatively recent interest in three-dimensional structure, the development of techniques used to label them has lagged behind parallel techniques used to label peptides and proteins. Therefore, this group`s discussion focused primarily on problems faced today in obtaining oligonucleotides labeled uniformly with carbon 13 and nitrogen 15.

  17. Polymersomes, smaller than you think: ferrocene as a TEM probe to determine core structure

    International Nuclear Information System (INIS)

    Johnston, A. H.; Dalton, P. D.; Newman, T. A.

    2010-01-01

    By incorporating ferrocene into the hydrophobic membrane of PEG-b-PCL polymersome nanoparticles it is possible to selectively visualize their core using Transmission Electron Microscopy (TEM). Two different sizes of ferrocene-loaded polymersomes with mean hydrodynamic diameters of approximately 40 and 90 nm were prepared. Image analysis of TEM pictures of these polymersomes found that the mean diameter of the core was 4-5 times smaller than the mean hydrodynamic diameter. The values obtained also allow the surface diameter and internal volume of the core to be calculated.

  18. Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors.

    Science.gov (United States)

    Wilhelm, M; Fishman, J A; Pontikis, R; Aubertin, A M; Wilhelm, F X

    2002-12-01

    Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA. We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors. Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovudine (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested.

  19. Vitamin E Phosphate Nucleoside Prodrugs: A Platform for Intracellular Delivery of Monophosphorylated Nucleosides

    Directory of Open Access Journals (Sweden)

    Richard Daifuku

    2018-02-01

    Full Text Available Vitamin E phosphate (VEP nucleoside prodrugs are designed to bypass two mechanisms of tumor resistance to therapeutic nucleosides: nucleoside transport and kinase downregulation. Certain isoforms of vitamin E (VE have shown activity against solid and hematologic tumors and result in chemosensitization. Because gemcitabine is one of the most common chemotherapeutics for the treatment of cancer, it was used to demonstrate the constructs utility. Four different VE isoforms were conjugated with gemcitabine at the 5′ position. Two of these were δ-tocopherol-monophosphate (MP gemcitabine (NUC050 and δ-tocotrienol-MP gemcitabine (NUC052. NUC050 was shown to be able to deliver gemcitabine-MP intracellularly by a nucleoside transport independent mechanism. Its half-life administered IV in mice was 3.9 h. In a mouse xenograft model of non-small cell lung cancer (NSCLC NCI-H460, NUC050 at a dose of 40 mg/kg IV qwk × 4 resulted in significant inhibition to tumor growth on days 11–31 (p < 0.05 compared to saline control (SC. Median survival was 33 days (NUC050 vs. 25.5 days (SC ((hazard ratio HR = 0.24, p = 0.017. Further, NUC050 significantly inhibited tumor growth compared to historic data with gemcitabine at 135 mg/kg IV q5d × 3 on days 14–41 (p < 0.05. NUC052 was administered at a dose of 40 mg/kg IV qwk × 2 followed by 50 mg/kg qwk × 2. NUC052 resulted in inhibition to tumor growth on days 14–27 (p < 0.05 and median survival was 34 days (HR = 0.27, p = 0.033. NUC050 and NUC052 have been shown to be safe and effective in a mouse xenograft of NSCLC.

  20. Meteorite-catalyzed synthesis of nucleosides and other prebiotic compounds

    Czech Academy of Sciences Publication Activity Database

    Ferus, Martin; Knížek, Antonín; Civiš, Svatopluk

    2015-01-01

    Roč. 112, č. 23 (2015), s. 7109-7110 ISSN 0027-8424 Institutional support: RVO:61388955 Keywords : meteorite-catalzzed synthesis * nucleosides * prebiotic compounds Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 9.423, year: 2015

  1. Spectroscopic Studies on the Effect of Some Ferrocene Derivatives in the Formation of Silver Nanoparticles.

    Science.gov (United States)

    Sanyal, Manik Kumar; Biswas, Bipul; Chowdhury, Avijit; Mallik, Biswanath

    2016-06-01

    Silver nanoparticles were prepared by microwave assisted method using silver nitrate as precursor in the presence of some ferrocene derivatives. The formation of the silver nanoparticles was monitored using UV-Vis spectroscopy. The UV-Vis spectroscopy revealed the formation of silver nanoparticles by exhibiting typical surface plasmon absorption band. The position of plasmon band (406-429 nm) was observed to depend on the nature of a particular ferrocene derivative used. TEM images indicated that the nanoparticles were spherical in shape and well-dispersed. Quantum dots (3.2 nm) were prepared by using ferrocenecarboxylic acid. The surface plasmon absorption band has shown red shift with increasing concentration of ferrocene derivative. For different duration of microwave heating time, intensity of absorption spectra in general was found to increase except in presence of ferrocene carbaldehyde where it decreased. Time-dependent spectra have indicated almost stable position of the surface plasmon band with increasing time of observation confirming that the as prepared silver nanoparticles did not aggregate with lapse of time.

  2. Selective Monoacylation of Ferrocene with Bulky Acylating Agents over Mesoporous Sieve AlKIT-5

    Czech Academy of Sciences Publication Activity Database

    Vitvarová, Dana; Voláková, Martina; Vlk, Josef; Vinu, A.; Štěpnička, P.; Čejka, Jiří

    2010-01-01

    Roč. 16, č. 26 (2010), s. 7773-7780 ISSN 0947-6539 R&D Projects: GA ČR GA104/07/0383; GA ČR GD203/08/H032 Institutional research plan: CEZ:AV0Z40400503 Keywords : acylation * aluminum * ferrocene Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.476, year: 2010

  3. Electrochemical studies of ferrocene in a lithium ion conducting organic carbonate electrolyte

    International Nuclear Information System (INIS)

    Laoire, Cormac O.; Plichta, Edward; Hendrickson, Mary; Mukerjee, Sanjeev; Abraham, K.M.

    2009-01-01

    We carried out a detailed study of the kinetics of oxidation of ferrocene (Fc) to ferrocenium ion (Fc + ) in the non-aqueous lithium ion conducting electrolyte composed of a solution of 1 M LiPF 6 in 1:1 EC:EMC solvent mixture. This study using cyclic (CV) and rotating disk electrode (RDE) voltammetry showed that the Fc 0 /Fc + redox couple is reversible in this highly concentrated electrolyte. The ferrocene and ferrocenium ion diffusion coefficients (D) were calculated from these results. In addition, the electron transfer rate constant (k 0 ) and the exchange current density for the oxidation of ferrocene were determined. A comparison of the kinetic data obtained from the two electrochemical techniques appears to show that the data from the RDE experiments are more reliable because they are collected under strict mass transport control. A Tafel slope of c.a. 79 mV/decade and a transfer coefficient α of 0.3 obtained from analysis of the RDE data for ferrocene oxidation suggest that the structure of the activated complex is closer to that of the oxidized specie due to strong interactions with the carbonate solvents. The experiments reported here are relevant to the study of redox reagents for the chemical overcharge protection of Li-ion batteries.

  4. A temperature induced ferrocene–ferrocenium interconversion in a ferrocene functionalized μ{sub 3}-O chromium carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Mereacre, Valeriu, E-mail: valeriu.mereacre@kit.edu [Institut für Anorganische Chemie, Karlsruher Institut für Technologie, D-76131 Karlsruhe (Germany); Schlageter, Martin [Institut für Nanotechnologie, Karlsruher Institut für Technologie, D-76344 Eggenstein-Leopoldshafen (Germany); Powell, Annie K., E-mail: annie.powell@kit.edu [Institut für Anorganische Chemie, Karlsruher Institut für Technologie, D-76131 Karlsruhe (Germany); Institut für Nanotechnologie, Karlsruher Institut für Technologie, D-76344 Eggenstein-Leopoldshafen (Germany)

    2015-05-01

    The infrared spectra and {sup 57}Fe Mössbauer measurements of a ferrocenecarboxylate functionalized {Cr_3O} complex in solid state are reported. It was established that conjugation of ferrocene Cp orbitals with the π orbitals of the adjacent carboxylic group stabilizes the trapped mixed-valence state leading to an intriguing coexistence of ferrocene and ferrocenium species giving rise to a new type of compound showing valence tautomerism in the solid state. - Highlights: • A stabilized ferrocene trapped mixed-valence state is reported. • New type of compound showing valence tautomerism in solid state. • A thermally induced electron transfer and a mixed-valence state near room temperature.

  5. New ferrocenic pyrrolo[1,2-a]quinoxaline derivatives: synthesis, and in vitro antimalarial activity.

    Science.gov (United States)

    Guillon, Jean; Moreau, Stéphane; Mouray, Elisabeth; Sinou, Véronique; Forfar, Isabelle; Fabre, Solene Belisle; Desplat, Vanessa; Millet, Pascal; Parzy, Daniel; Jarry, Christian; Grellier, Philippe

    2008-10-15

    Following our search for antimalarial compounds, novel series of ferrocenic pyrrolo[1,2-a]quinoxaline derivatives 1-2 were synthesized from various substituted nitroanilines and tested for in vitro activity upon the erythrocytic development of Plasmodiumfalciparum strains with different chloroquine-resistance status. The pyrrolo[1,2-a]quinoxalines 1 were prepared in 6-8 steps through a regioselective palladium-catalyzed monoamination by coupling 4-chloropyrrolo[1,2-a]quinoxalines with 1,3-bis(aminopropyl)piperazine or -methylamine using Xantphos as the ligand. The ferrocenic bispyrrolo[1,2-a]quinoxalines 2 were prepared by reductive amination of previously described bispyrrolo[1,2-a]quinoxalines 9 with ferrocene-carboxaldehyde, by treatment with NaHB(OAc)(3). The best results were observed with ferrocenic pyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus and no substitution on the terminal N-ferrocenylmethylamine function enhanced the pharmacological activity. Selected compounds 1b, 1f-h, 1l and 2a were tested for their ability to inhibit beta-haematin formation, the synthetic equivalent of hemozoin, by using the HPIA (heme polymerization inhibitory activity) assay. Of the tested compounds, only 2a showed a beta-haematin formation inhibition, but no inhibition of haem polymerization was observed with the other selected ferrocenic monopyrrolo[1,2-a]quinoxaline derivatives 1b, 1f-h and 1l, as the IC(50) values were superior to 10 equivalents.

  6. Facile route of biopolymer mediated ferrocene (FO) nanoparticles in aqueous dispersion

    Energy Technology Data Exchange (ETDEWEB)

    Kaus, Noor Haida Mohd., E-mail: noorhaida@usm.my [School of Chemical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia and Centre for Organized Matter Chemistry, School of Chemistry, Cantock' s Close, BS8 1TS, Bristol (United Kingdom); Collins, A. M.; Mann, S. [Centre for Organized Matter Chemistry, School of Chemistry, Cantock' s Close, BS8 1TS, Bristol (United Kingdom)

    2014-10-24

    In this paper, we present a facile method for production stable aqueous dispersion of ferrocene (FO) nanoparticles. Ferrocene compounds were employed to achieve stable nanodispersions, stabilized with three different biopolymers namely, alginate, CM-dextran and chitosan. The nanoparticles produce are spherical, less than 10 nm in mean diameter and highly stable without any sedimentation. Fourier infrared transform (FTIR) and X-ray diffraction (XRD) studies confirmed the purity of ferrocene nanoparticles there is no modifications occur during the preparation route. FTIR spectra results were consistent with the presence of absorption band of cyclopentadienyl ring (C{sub 5}H{sub 5}{sup −} ion) which assigned to ν(C-C) vibrations (1409 cm-1), δ(C-H) stretching at 1001 cm{sup −1} and π(C-H) vibrations at 812 cm{sup −1}. Furthermore, all functional group for biopolymers such as CO from carboxyl group of CM-dextran and sodium alginate appears at 1712 cm{sup −1} and 1709 cm{sup −1} respectively, indicating there are steric repulsion interactions for particles stabilization. Powder X-ray diffraction patterns of sedimented samples of the biopolymers-stabilized ferrocene (FO) showed all reflections which were indexed respectively to the (−110), (001), (−201), (−111), (200), (−211), (210), (120) and (111) according to the monoclinic phase ferrocene. This confirmed that the products obtained were of high purity of Fe and EDAX analysis also suggests that the presence of the Fe element in the colloidal dispersion.

  7. Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.

    Science.gov (United States)

    Kellner, Stefanie; Kollar, Laura Bettina; Ochel, Antonia; Ghate, Manjunath; Helm, Mark

    2013-01-01

    Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions.

  8. New insights into the synergism of nucleoside analogs with radiotherapy

    International Nuclear Information System (INIS)

    Lee, Michael W; Parker, William B; Xu, Bo

    2013-01-01

    Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells

  9. Synthesis and Antiviral Activity of 3-Aminoindole Nucleosides of 2-Acetamido-2-deoxy-D-glucose

    Energy Technology Data Exchange (ETDEWEB)

    Abdelrahman, Adel A. H.; Elessawy, Farag A.; Barakat, Yousif A. [Menoufia Univ., Shebin El-Koam (Egypt); Ellatif, Mona M. Abd [The British Univ. in Egypt, Cairo (Egypt)

    2012-10-15

    A new method for the construction of 3-aminoindole nucleosides of 2-acetamido-2-deoxy-D-glucose based is presented. Nitration and acetylation of the indole nucleosides by acetic anhydride-nitric acid mixture followed by reduction using silver catalyst (SNSM) impregnated on silica gel, afforded the corresponding amino indole nucleosides. The nucleosides were tested for antiviral activity against hepatitis B virus (HBV) to show different degrees of antiviral activities or inhibitory actions.

  10. Ionic interactions in electroactive self-assembled monolayers of ferrocene species

    Science.gov (United States)

    Delong, Hugh C.; Donohue, John J.; Buttry, Daniel A.

    1991-04-01

    The electrochemical and interfacial behavior of two types of electroactive self-assembled monolayer systems is investigated at gold electrodes. The first type is a ferrocene-based surfactant (a redox surfactant) derived from (dimethylamino)methylferrocene via quaternization of the amino group with various n-alkylbromides. These have a long alkyl chain with 16 or 18 carbons in the chain pendent from the cationic ammonium group. These are referred to as C16 and C18. The second type is a ferrocene-based dimeric species with a disulfide functional group capable of providing a permanent anchor to the Au electrode, thus endowing monolayers of this species with exceptional stability towards desorption. The electrochemical quartz crystal microbalance (EQM) is used to monitor the mass changes which occur at the electrode surface during the redox processes of these two species.

  11. Redox control of rotary motions in ferrocene-based elemental ball bearings.

    Science.gov (United States)

    Iordache, Adriana; Oltean, Mircea; Milet, Anne; Thomas, Fabrice; Baptiste, Benoît; Saint-Aman, Eric; Bucher, Christophe

    2012-02-08

    Rotational motions of ferrocene-based carousels have been achieved by electron transfer centered on π-dimerizable 4,4'-bipyridinium substituents introduced on both cyclopentadienyl rings through covalent linkers of different size, geometry, and flexibility. Detailed spectroscopic, electrochemical, and theoretical analyses demonstrate that rigid and fully conjugated linkers allow the quantitative formation of intramolecular π-dimers resulting from optimized orbital overlaps within the HOMO of the electrochemically generated bis-radical species. The tetra-cationic "charge-repelled" conformers, the self-assembled π-dimers, and their electron triggered interconversions have been investigated by UV-vis, NMR, and ESR spectroscopy, electrochemistry, X-ray diffraction analysis, and theoretical calculations. These studies support the conclusion that the rotation of both cyclopentadienyl rings in ferrocene can be controlled electrochemically using noncovalent reversible interactions arising from π-radical coupling processes.

  12. Hybrid Organometallic-Inorganic Nanomaterial: Acetyl Ferrocene Schiff base Immobilized on Silica Coated Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    M. Masteri-Farahani

    2015-10-01

    Full Text Available In  this  work,  a  new  hybrid  organometallic-inorganic  hybrid nanomaterial was prepared by immobilization of acetyl ferrocene on the  surface  of magnetite  nanoparticles. Covalent  grafting of silica coated magnetite nanoparticles (SCMNPs with 3-aminopropyl triethoxysilane gave aminopropyl-modified magnetite nanoparticles (AmpSCMNPs. Then, Schiff base condensation  of AmpSCMNPs with acetyl  ferrocene resulted in the preparation of acferro-SCMNPs hybrid nanomaterial. Characterization of the prepared nanomaterial was performed with different physicochemical methods such as Fourier transform infrared spectroscopy (FT-IR, X-ray diffraction (XRD, vibrating sample magnetometry (VSM, thermogravimetric analysis (TGA, scanning electron microscopy (SEM, and transmission electron microscopy (TEM. VSM analysis showed superparamagnetic properties of the prepared nanomaterial and TEM and SEM analyses indicated the relatively spherical nanoparticles with 15 nm average size.

  13. Control of Helical Chirality of Ferrocene-Dipeptide Conjugates by the Secondary Structure of Dipeptide Chains.

    Science.gov (United States)

    Moriuchi, Toshiyuki; Nishiyama, Taiki; Nobu, Masaki; Hirao, Toshikazu

    2017-09-18

    Controlling helical chirality and creating protein secondary structures in cyclic/acyclic ferrocene-dipeptide bioorganometallic conjugates were achieved by adjusting the conformational flexibility of the dipeptide chains. In systems reported to date, the helical chirality of a conjugate was determined by the absolute configuration of the adjacent amino acid reside. In contrast, it was possible to induce both M- and P-helical chirality, even when the configuration of the adjacent amino acid was the same. It is particularly interesting to note that M-helical chirality was produced in a cyclic ferrocene-dipeptide conjugate composed of the l-Ala-d-Pro-cystamine-d-Pro-l-Ala dipeptide sequence (1), in which a type II β-turn-like secondary structure was established. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years

    Directory of Open Access Journals (Sweden)

    Hanadi Sinokrot

    2017-10-01

    Full Text Available Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally, VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and non-nucleoside analogues prodrugs, the most promising are nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues have witnessed productive era in the recent past few years. The era of non-interferon based treatment of hepatitis (through direct inhibitors of NS5A has dawned.

  15. Deoxyribonucleoside kinases activate nucleoside antibiotics in severely pathogenic bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Shannon, O.; Clausen, A.R.

    2007-01-01

    Common bacterial pathogens are becoming progressively more resistant to traditional antibiotics, representing a major public-health crisis. Therefore, there is a need for a variety of antibiotics with alternative modes of action. In our study, several nucleoside analogs were tested against pathog...... alternative for combating pathogenic bacteria.......Common bacterial pathogens are becoming progressively more resistant to traditional antibiotics, representing a major public-health crisis. Therefore, there is a need for a variety of antibiotics with alternative modes of action. In our study, several nucleoside analogs were tested against...... pathogenic staphylococci and streptococci. We show that pyrimidine-based nucleoside analogs, like 3'-azido-3'-deoxythymidine (AZT) and 2',2'-difluoro-2'deoxycytidine (gemcitabine), are specifically activated by the endogenous bacterial deoxyribonucleoside kinases, leading to cell death. Deoxyribonucleoside...

  16. Synthesis of O-Amino Sugars and Nucleosides

    Directory of Open Access Journals (Sweden)

    Na Chen

    2018-03-01

    Full Text Available Nucleic acids and carbohydrates are essential biomolecules involved in numerous biological and pathological processes. Development of multifunctional building blocks based on nucleosides and sugars is in high demand for the generation of novel oligonucleotide mimics and glycoconjugates for biomedical applications. Recently, aminooxyl-functionalized compounds have attracted increasing research interest because of their easy derivatization through oxime ligation or N-oxyamide formation reactions. Various biological applications have been reported for O-amino carbohydrate- and nucleoside-derived compounds. Here, we report our efforts in the design and synthesis of glyco-, glycosyl, nucleoside- and nucleo-aminooxy acid derivatives from readily available sugars and amino acids, and their use for the generation of N-oxyamide-linked oligosaccharides, glycopeptides, glycolipids, oligonucleosides and nucleopeptides as novel glycoconjugates or oligonucleotide mimics. Delicate and key points in the synthesis will be emphasized.

  17. Oxidation of ferrocene by thiocyanic acid in the presence of ammonium oxalate

    Science.gov (United States)

    Ruslin, Farah bt; Yamin, Bohari M.

    2014-09-01

    A flake-like crystalline salt was obtained from the reaction of ferrocene, oxalic acid and ammonium thiocyanate in ethanol The elemental analysis and spectroscopic data were in agreement with the preliminary X-ray molecular structure. The compound consists of four ferrocenium moieties and a counter anion consisting of two (tetraisothiocyanato)iron(III) linked by an oxalato bridging group in such a way that both iron central atoms adopt octahedral geometries.

  18. Study of ferrocene dicarboxylic acid on substrates of varying chemical activity

    Czech Academy of Sciences Publication Activity Database

    Berger, Jan; Kośmider, K.; Stetsovych, Oleksandr; Vondráček, Martin; Hapala, Prokop; Spadafora, Evan; Švec, Martin; Jelínek, Pavel

    2016-01-01

    Roč. 120, č. 38 (2016), 21955-21961 ISSN 1932-7447 R&D Projects: GA ČR(CZ) GA14-02079S; GA ČR GB14-37427G; GA MŠk(CZ) LG15050; GA MŠk LM2015088 Institutional support: RVO:68378271 Keywords : ferrocene * nc-AFM * DFT * STM * XPS * NEXAFS Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 4.536, year: 2016

  19. Nucleoside analogues are activated by bacterial deoxyribonucleoside kinases in a species-specific manner

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, Anders; On, Stephen L. W.

    2007-01-01

    To investigate the bactericidal activity of antiviral and anticancer nucleoside analogues against a variety of pathogenic bacteria and characterize the activating enzymes, deoxyribonucleoside kinases (dNKs). Several FDA-approved nucleoside analogue drugs were screened for their potential bacteric......-specific manner. Therefore, nucleoside analogues have a potential to be employed as antibiotics in the fight against emerging multiresistant bacteria....

  20. Area, age and gender dependence of the nucleoside system in the brain: a review of current literature.

    Science.gov (United States)

    Kovács, Zsolt; Juhász, Gábor; Palkovits, Miklós; Dobolyi, Arpád; Kékesi, Katalin A

    2011-01-01

    Nucleosides, such as uridine, inosine, guanosine and adenosine, may participate in the regulation of sleep, cognition, memory and nociception, the suppression of seizures, and have also been suggested to play a role in the pathophysiology of some neurodegenerative and neuropsychiatric diseases. Under pathological conditions, levels of nucleosides change extremely in the brain, indicating their participation in the pathophysiology of disorders like Alzheimer's disease, Parkinson's disease and schizophrenia. These findings have resulted in an increasing attention to the roles of nucleosides in the central nervous system. The specific effects of nucleosides depend on the expression of their receptors and transporters in neuronal and glial cells, as well as their extracellular concentrations in the brain. A complex interlinked metabolic network and transporters of nucleosides may balance nucleoside levels in the brain tissue under normal conditions and enable the fine modulation of neuronal and glial processes via nucleoside receptor signaling mechanisms. Brain levels of nucleosides were found to vary when measured in a variety of different brain regions. In addition, nucleoside levels also depend on age and gender. Furthermore, distributions of nucleoside transporters and receptors as well as nucleoside metabolic enzyme activities demonstrate the area, age and gender dependence of the nucleoside system, suggesting different roles of nucleosides in functionally different brain areas. The aim of this review article is to summarize our present knowledge of the area-, age- and gender-dependent distribution of nucleoside levels, nucleoside metabolic enzyme activity, nucleoside receptors and nucleoside transporters in the brain.

  1. Functional characterization of a recombinant sodium-dependent nucleoside transporter with selectivity for pyrimidine nucleosides (cNT1rat) by transient expression in cultured mammalian cells.

    OpenAIRE

    Fang, X; Parkinson, F E; Mowles, D A; Young, J D; Cass, C E

    1996-01-01

    We have demonstrated that monkey kidney (COS-1) cells have a single type of nucleoside transport process, which, because it was equilibrative, sodium-independent and could be inhibited by nitrobenzylthioinosine (NBMPR), was identified as the 'equilibrative sensitive' or 'es' transporter. Using NBMPR or dilazep to inhibit the endogenous nucleoside transport activity, we have transiently expressed a cDNA that encodes an inhibitor-insensitive, concentrative nucleoside transporter protein (cNT1ra...

  2. Synthesis of (Purin-6-yl)methylphosphonate Bases and Nucleosides

    Czech Academy of Sciences Publication Activity Database

    Hasník, Zbyněk; Pohl, Radek; Hocek, Michal

    2010-01-01

    Roč. 51, č. 18 (2010), s. 2464-2466 ISSN 0040-4039 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : purines * nucleosides * phosphonates * cross-coupling Subject RIV: CC - Organic Chemistry Impact factor: 2.618, year: 2010

  3. Amino Acid Ester Prodrugs of Nucleoside and Nucleotide Antivirals

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela

    2017-01-01

    Roč. 17, č. 10 (2017), s. 818-833 ISSN 1389-5575 Grant - others:AV ČR(CZ) M200551201 Institutional support: RVO:61388963 Keywords : acyclic nucleoside analogues * antiherpetics * antiretrovirals * cidofovir * peptidomimetics * prodrugs Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.661, year: 2016

  4. Antiviral acyclic nucleoside phosphonates: New structures and prodrugs

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Tichý, Tomáš; Pomeisl, Karel; Andrei, G.; Balzarini, J.; Snoeck, R.

    2016-01-01

    Roč. 1, č. 2 (2016), s. 37 [PharmaMed-2016. International Conference on Medicinal and Pharmaceutical Chemistry . 05.12.2016-07.12.2016, Dubai] R&D Projects: GA ČR(CZ) GA14-00522S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * prodrugs * antivirals * 5-azacytosine Subject RIV: CC - Organic Chemistry

  5. Two convergent approaches toward novel carbocyclic C-nucleosides

    Czech Academy of Sciences Publication Activity Database

    Nencka, Radim; Šála, Michal; Dejmek, Milan; Dračínský, Martin; Holý, Antonín; Hřebabecký, Hubert

    -, č. 23 (2010), s. 4119-4130 ISSN 0039-7881 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : carbocyclic C-nucleosides * convergent approach * uracil * pyrimidines Subject RIV: CC - Organic Chemistry Impact factor: 2.260, year: 2010

  6. Efficient synthesis and biological properties of the 2‘-trifluoromethyl analogues of acyclic nucleosides and acyclic nucleoside phosphonates

    Czech Academy of Sciences Publication Activity Database

    Jansa, Petr; Kolman, Viktor; Kostinová, Alexandra; Dračínský, Martin; Mertlíková-Kaiserová, Helena; Janeba, Zlatko

    2011-01-01

    Roč. 76, č. 10 (2011), s. 1187-1198 ISSN 0010-0765 R&D Projects: GA MV VG20102015046 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * nucleotides * phosphorus * fluorine * biological activity * antibiotics Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  7. Unusual metal-ligand charge transfer in ferrocene functionalized μ3-O iron carboxylates observed with Mössbauer spectroscopy

    International Nuclear Information System (INIS)

    Mereacre, Valeriu; Schlageter, Martin; Eichhöfer, Andreas; Bauer, Thomas; Wolny, Juliusz A.; Schünemann, Volker; Powell, Annie K.

    2016-01-01

    Temperature dependent Mössbauer studies of two ferrocenecarboxylate functionalized {Fe 3 O} complexes in solid state are reported. It was found that conjugation of ferrocene ring orbitals with the π orbitals of the adjacent carboxylic group promotes a shift of electron density from the ferrocene Fe II ion to the cyclopentadienide rings with π-orbital character giving rise to a new type of mixed-valence compound. - Highlights: • In this manuscript we describe a mechanism of electron density shift which stabilizes the trapped mixed-valence state. • The coexistence of ferrocene and ferrocenium in solid state was determined. • A mixed-valence state at room-temperature and a thermally induced electron transfer with gradual interconversion were observed.

  8. Direct observation of electronic and nuclear ground state splitting in external magnetic field by inelastic neutron scattering on oxidized ferrocene and ferrocene containing polymers

    Science.gov (United States)

    Appel, Markus; Frick, Bernhard; Elbert, Johannes; Gallei, Markus; Stühn, Bernd

    2015-01-01

    The quantum mechanical splitting of states by interaction of a magnetic moment with an external magnetic field is well known, e.g., as Zeeman effect in optical transitions, and is also often seen in magnetic neutron scattering. We report excitations observed in inelastic neutron spectroscopy on the redox-responsive polymer poly(vinylferrocene). They are interpreted as splitting of the electronic ground state in the organometallic ferrocene units attached to the polymer chain where a magnetic moment is created by oxidation. In a second experiment using high resolution neutron backscattering spectroscopy we observe the hyperfine splitting, i.e., interaction of nuclear magnetic moments with external magnetic fields leading to sub-μeV excitations observable in incoherent neutron spin-flip scattering on hydrogen and vanadium nuclei.

  9. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens D; Pedersen, Court

    2003-01-01

    BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ... the long-term consequences of triple class HAART regimens, including the development of broad drug resistance....

  10. Electrochemistry of a ferrocene-grafted cell-penetrating peptide

    International Nuclear Information System (INIS)

    Messina, Pierluca; Hallais, Géraldine; Labbé, Eric; Béranger, Marie; Chassaing, Gérard; Lavielle, Solange; Mansuy, Christelle; Buriez, Olivier

    2012-01-01

    A cationic cell-penetrating peptide (CPP) labeled with both a ferrocenyl (Fc) moiety and a biotin (B) was successfully synthesized and investigated by electrochemistry. This original CPP derivative noted as Fc-CPP-B could be electrochemically detected, at a micromolar concentration, at a naked gold bead electrode. The presence of a biotin tag in the Fc-CPP-B complex allowed its complexation with avidin, which was itself tethered to a thiolated self-assembled monolayer. Such an avidin-modified gold surface, characterized by atomic force microscopy (AFM), allowed the immobilization of Fc-CPP-B onto the electrode surface, which greatly enhanced its electrochemical detection. Nevertheless, under these conditions the electrogenerated ferrocenium cation could not be reduced during the backward scan, indicating its unexpected reactivity when tethered within the avidin environment. In terms of detection and redox probe regeneration the best results were obtained at a glassy carbon electrode modified with a cation-exchange polymer. Ion-exchange voltammetry, performed under these conditions, allowed the pre-concentration of the peptide at the electrode surface thanks to the net positive charge of the CPP derivative. Interestingly, the anionic character of the polymer contributed to retain the electrogenerated cation Fc + in the film so that it could be reduced back to its original neutral form during the reverse voltammetric scans.

  11. Effect of surface area of substrates aiming the optimization of carbon nanotube production from ferrocene

    International Nuclear Information System (INIS)

    Osorio, A.G.; Bergmann, C.P.

    2013-01-01

    Highlights: ► An optimized synthesis of CNTs by ferrocene is proposed. ► The surface area of substrates influences the nucleation of CNTs. ► The higher the surface area of substrates the lower the temperature of synthesis. ► Chemical composition of substrates has no influence on the growth of CNTs. - Abstract: Ferrocene is widely used for the synthesis of carbon nanotubes due to its ability to act as catalyst and precursor of the synthesis. This paper proposes an optimization of the synthesis of carbon nanotubes from ferrocene, using a substrate with high surface area for their nucleation. Four different surface areas of silica powder were tested: 0.5, 50, 200 and 300 m 2 /g. Raman spectroscopy and microscopy were used to characterize the product obtained and X-ray diffraction and thermal analysis were also performed to evaluate the phases of the material. It was observed that the silica powder with the highest surface area allowed the synthesis of carbon nanotubes to occur at a lower temperature (600 °C), whereas substrates with a surface area lower than 50 m 2 /g will only form carbon nanotubes at temperatures higher than 750 °C. In order to evaluate the influence of chemical composition of the substrate, three different ceramic powders were analyzed: alumina, silica and zirconia. carbon black and previously synthesized carbon nanotubes were also used as substrate for the synthesis and the results showed that the chemical composition of the substrate does not play a relevant role in the synthesis of carbon nanotubes, only the surface area showed an influence.

  12. All-Plastic Electrochemical Transistor for Glucose Sensing Using a Ferrocene Mediator

    Directory of Open Access Journals (Sweden)

    George G. Malliaras

    2009-12-01

    Full Text Available We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene doped with poly(styrene sulfonate (PEDOT:PSS. The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva.

  13. Covalent functionalization of few-wall carbon nanotubes by ferrocene derivatives for bioelectrochemical devices

    Energy Technology Data Exchange (ETDEWEB)

    Allali, Naoual [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement, UMR 7564 CNRS-Universite de Lorraine, 54602 Villers-les-Nancy (France); Laboratoire de Structure et Reactivite des Systemes Moleculaires Complexes, UMR 7565 CNRS-Universite de Lorraine, 54506 Vandoeuvre-les-Nancy (France); Department of Engineering Sciences and Mathematics, Luleaa University of Technology, 97187 Luleaa (Sweden); Urbanova, Veronika; Waldbock, Jeremy; Etienne, Mathieu; Mallet, Martine; Walcarius, Alain; Dossot, Manuel [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement, UMR 7564 CNRS-Universite de Lorraine, 54602 Villers-les-Nancy (France); Mamane, Victor; Fort, Yves [Laboratoire de Structure et Reactivite des Systemes Moleculaires Complexes, UMR 7565 CNRS-Universite de Lorraine, 54506 Vandoeuvre-les-Nancy (France); Devaux, Xavier [Insitut Jean Lamour, Department P2M, UMR 7198 CNRS-Universite de Lorraine, Ecole des Mines, 54042 Nancy (France); Vigolo, Brigitte; McRae, Edward [Insitut Jean Lamour, Department CP2S, UMR 7198 CNRS-Universite de Lorraine, 54506 Vandoeuvre-les-Nancy (France); Noel, Maxime [Department of Engineering Sciences and Mathematics, Luleaa University of Technology, 97187 Luleaa (Sweden); Soldatov, Alexander V. [Department of Engineering Sciences and Mathematics, Luleaa University of Technology, 97187 Luleaa (Sweden); Department of Physics, Harvard University, Cambridge, MA 02138 (United States)

    2012-12-15

    The present work reports the covalent functionalization of few-wall CNTs (FWCNTs) by ferrocene derivatives to (i) improve their dispersion efficiency in water and (ii) graft electroactive chemical groups on their side-walls in order to promote electron transfer to biomolecules. The functionalized CNTs (f-CNTs) are used to modify a glassy carbon electrode and this modified electrode is used for oxidizing the cofactor NADH (dihydronicotinamide adenine dinucleotide). (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. Improving cytotoxic properties of ferrocenes by incorporation of saturated N-heterocycles

    Czech Academy of Sciences Publication Activity Database

    Hodík, Tomáš; Lamač, Martin; Červenková Šťastná, Lucie; Cuřínová, Petra; Karban, Jindřich; Skoupilová, H.; Hrstka, R.; Císařová, I.; Gyepes, Robert; Pinkas, Jiří

    2017-01-01

    Roč. 846, OCT 2017 (2017), s. 141-151 ISSN 0022-328X R&D Projects: GA ČR(CZ) GAP207/12/2368; GA ČR(CZ) GA17-05838S Institutional support: RVO:61388955 ; RVO:67985858 Keywords : metallodrugs * ferrocene derrivatives * N-heterocycles Subject RIV: CF - Physical ; Theoretical Chemistry; CF - Physical ; Theoretical Chemistry (UCHP-M) OBOR OECD: Inorganic and nuclear chemistry; Physical chemistry (UCHP-M) Impact factor: 2.184, year: 2016

  15. Crystal structure of cyclic tris(ferrocene-1,1′-diyl

    Directory of Open Access Journals (Sweden)

    Ruslan Shekurov

    2014-09-01

    Full Text Available The molecular structure of the trinuclear title compound, [Fe3(C10H83] {systematic name: tris[μ-(η5:η5-1,1′-bicyclopentadienyl]triiron(II}, consists of three ferrocene subunits (each with an eclipsed conformation that are condensed via C—C bonds of the fulvalene moieties into a cyclic trimer. The angles between the planes of the cyclopentadienyl (Cp rings within the three fulvalene moieties are 76.1 (3, 80.9 (3 and 81.7 (3°. In the crystal, C—H...π interactions between neighbouring molecules lead to the cohesion of the structure.

  16. A new approach to ferrocene derived alkenes via copper-catalyzed olefination

    Directory of Open Access Journals (Sweden)

    Vasily M. Muzalevskiy

    2015-11-01

    Full Text Available A new approach to ferrocenyl haloalkenes and bis-alkenes was elaborated. The key procedure involves copper catalyzed olefination of N-unsubstituted hydrazones, obtained from ferrocene-containing carbonyl compounds and hydrazine, with polyhaloalkanes. The procedure is simple, cheap and could be applied for the utilization of environmentally harmful polyhalocarbons. The cyclic voltammetry study of the representative examples of the synthesized ferrocenyl alkenes shows the strong dependence of the cathodic behavior on the amount of vinyl groups: while for the monoalkene containing molecules no reduction is seen, the divinyl products are reduced in several steps.

  17. A new approach to ferrocene derived alkenes via copper-catalyzed olefination.

    Science.gov (United States)

    Muzalevskiy, Vasily M; Shastin, Aleksei V; Demidovich, Alexandra D; Shikhaliev, Namiq G; Magerramov, Abel M; Khrustalev, Victor N; Rakhimov, Rustem D; Vatsadze, Sergey Z; Nenajdenko, Valentine G

    2015-01-01

    A new approach to ferrocenyl haloalkenes and bis-alkenes was elaborated. The key procedure involves copper catalyzed olefination of N-unsubstituted hydrazones, obtained from ferrocene-containing carbonyl compounds and hydrazine, with polyhaloalkanes. The procedure is simple, cheap and could be applied for the utilization of environmentally harmful polyhalocarbons. The cyclic voltammetry study of the representative examples of the synthesized ferrocenyl alkenes shows the strong dependence of the cathodic behavior on the amount of vinyl groups: while for the monoalkene containing molecules no reduction is seen, the divinyl products are reduced in several steps.

  18. Synthesis and NMR of {sup 15}N-labeled DNA fragments

    Energy Technology Data Exchange (ETDEWEB)

    Jones, R.A. [Rutgers, The State Univ. of New Jersey, Piscataway, NJ (United States)

    1994-12-01

    DNA fragments labeled with {sup 15}N at the ring nitrogens and at the exocyclic amino groups can be used to obtain novel insight into interactions such as base pairing, hydration, drug binding, and protein binding. A number of synthetic routes to {sup 15}N-labeled pyrimidine nucleosides, purines, and purine nucleosides have been reported. Moreover, many of these labeled bases or monomers have been incorporated into nucleic acids, either by chemical synthesis or by biosynthetic procedures. The focus of this chapter will be on the preparation of {sup 15}N-labeled purine 2{prime}-deoxynucleosides, their incorporation into DNA fragments by chemical synthesis, and the results of NMR studies using these labeled DNA fragments.

  19. Food Labels

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Food Labels KidsHealth / For Teens / Food Labels What's in ... to have at least 95% organic ingredients. Making Food Labels Work for You The first step in ...

  20. C-Nucleosides: Synthetic Strategies and Biological Applications

    Czech Academy of Sciences Publication Activity Database

    Štambaský, J.; Hocek, Michal; Kočovský, P.

    2009-01-01

    Roč. 109, č. 12 (2009), s. 6729-6764 ISSN 0009-2665 R&D Projects: GA MŠk LC512; GA AV ČR IAA400550902 Grant - others:NIH(US) 1R03TW007372-01 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * nucleobases * biological activity * extension of genetic alphabet Subject RIV: CC - Organic Chemistry Impact factor: 35.957, year: 2009

  1. Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery

    Science.gov (United States)

    Benizri, Sebastien; Ferey, Ludivine; Alies, Bruno; Mebarek, Naila; Vacher, Gaelle; Appavoo, Ananda; Staedel, Cathy; Gaudin, Karen; Barthélémy, Philippe

    2018-01-01

    Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low water solubility (drug. In this context, the use of nanocarriers is currently investigated in order to overcome these drawbacks. In this contribution, we report a new type of sorafenib-based nanoparticles stabilized by hybrid nucleoside-lipids. The solid lipid nanoparticles (SLNs) showed negative or positive zeta potential values depending on the nucleoside-lipid charge. Transmission electron microscopy of sorafenib-loaded SLNs revealed parallelepiped nanoparticles of about 200 nm. Biological studies achieved on four different cell lines, including liver and breast cancers, revealed enhanced anticancer activities of Sorafenib-based SLNs compared to the free drug. Importantly, contrast phase microscopy images recorded after incubation of cancer cells in the presence of SLNs at high concentration in sorafenib (> 80 μM) revealed a total cancer cell death in all cases. These results highlight the potential of nucleoside-lipid-based SLNs as drug delivery systems.

  2. Chemical and morphological changes during production of conducting carbons from ferrocene-poly (furfuryl alcohol)

    International Nuclear Information System (INIS)

    Ozaki, J.; Cashion, J.D.; Brown, L.J.

    1996-01-01

    Carbons are obtained by heating organic substances up to 1000 deg C under inert atmosphere. The electronic properties of carbons change dramatically during this carbonisation process. By controlled preparation, it is possible to obtain electronically functional materials. The addition of iron to the organic starting material has a strong modifying effect and, in particular, carbonising a ferrocene-poly(furfuryl alcohol) (PFA) mixture at 700 deg C produces a carbon with a comparable electron transfer rate to platinum. 57 Moessbauer spectra showed that the first transformation of the ferrocene is to magnetite, at 200-300 deg C. At 600 deg C, the magnetite is converted to wustite, while at 650 deg C α-iron starts to appear. The final products at 800 deg C were α-iron, γ-iron and cementite, Fe 3 C. Morphological changes were studied by SEM. The tentative explanation for these results is that the iron promotes the elimination of oxygen from the initial PFA structure to produce magnetite. At 600-650 deg C , the magnetite is carbothermically reduced to wustite and α-iron, forming glassy carbon. Above 700 deg C, the iron dissolves carbon atoms to make a solid solution. On cooling, some of this fractionates into graphitic carbon, cementite and γ-iron stabilised by the carbon atoms. We believe that the furry surface is produced in this cooling process

  3. Chemical and morphological changes during production of conducting carbons from ferrocene-poly (furfuryl alcohol)

    Energy Technology Data Exchange (ETDEWEB)

    Ozaki, J [Tohoku University, Sendai, Japan (Japan). Institute of Chemical Reaction Science; Cashion, J D; Brown, L J [Monash Univ., Clayton, VIC (Australia). Dept. of Physics

    1997-12-31

    Carbons are obtained by heating organic substances up to 1000 deg C under inert atmosphere. The electronic properties of carbons change dramatically during this carbonisation process. By controlled preparation, it is possible to obtain electronically functional materials. The addition of iron to the organic starting material has a strong modifying effect and, in particular, carbonising a ferrocene-poly(furfuryl alcohol) (PFA) mixture at 700 deg C produces a carbon with a comparable electron transfer rate to platinum. {sup 57} Moessbauer spectra showed that the first transformation of the ferrocene is to magnetite, at 200-300 deg C. At 600 deg C, the magnetite is converted to wustite, while at 650 deg C {alpha}-iron starts to appear. The final products at 800 deg C were {alpha}-iron, {gamma}-iron and cementite, Fe{sub 3}C. Morphological changes were studied by SEM. The tentative explanation for these results is that the iron promotes the elimination of oxygen from the initial PFA structure to produce magnetite. At 600-650 deg C , the magnetite is carbothermically reduced to wustite and {alpha}-iron, forming glassy carbon. Above 700 deg C, the iron dissolves carbon atoms to make a solid solution. On cooling, some of this fractionates into graphitic carbon, cementite and {gamma}-iron stabilised by the carbon atoms. We believe that the furry surface is produced in this cooling process

  4. FT-IR, NMR spectroscopic and quantum mechanical investigations of two ferrocene derivatives

    Directory of Open Access Journals (Sweden)

    Ö. Alver

    2017-07-01

    Full Text Available New ferrocene derivatives as N-(3-piperidin-1-ylpropylferrocenamide (Fc-3ppa and N-(pyridine-3-ylmethylferrocenamide (Fc-3pica and structural investigations were carried out with 1H, 13C, DEPT 45 or 135, HETCOR, COSY NMR and FT-IR spectroscopic techniques. Characterization of Fc-3ppa (FeC19H26N2O and Fc-3pica (FeC17H16N2O was also supported by density functional theory (DFT used by B3LYP functional and 6-31G(d or 6-311++G(d,p basis sets. From the combination of all the results, it can be clearly seen that syntheses of Fc-3ppa and Fc-3pica have been successfully achieved. Theoretical values are successfully compared against experimental data and B3LYP method is able to provide satisfactory results for predicting NMR properties and vibrational frequencies of the synthesized ferrocene based systems.

  5. Correlation of Spectral and Electrochemical Properties of a Series of Ferrocene Derivatives

    Science.gov (United States)

    Hepp, Aloysius F.; Wrighton, Mark S.

    2016-01-01

    Charge-transfer-to-solvent (CTTS) bands are observed in the UV/VIS spectra of a series of ferrocene derivatives (ferrocene; 1,1'-dimethyl; 1,2,3,4,5-pentamethyl; 1,2,3,4,l',2',3',4'-octamethyl; and decamethyl) by the addition of increasing amounts of CCl4 to ethanol solutions. A linear correlation (slope = 8540 cm-1/V) was found between the redox potential and the energy of the CTTS band, consistent with electrochemical and photochemical oxidation by removal of an electron from the same molecular orbital. Inclusion of literature data for ruthenocene and [(?5-C5H5)Fe(CO)]4 results in a line with a slope of 8140 cm-1/V, within 1 percent of the wavenumber to electron volt conversion factor. Calculation of association constants (K) shows a slight decrease (1.2 to 0.7 mole fraction-1) as the bulkiness of the cyclopentadienyl ring increases, consistent with either a steric or a repulsive electronic effect. The extinction coefficient of the CTTS absorption was constant at approximately 1700/M/cm.

  6. Retained sensitivity to cytotoxic pyrimidine nucleoside analogs in thymidine kinase 2 deficient human fibroblasts

    OpenAIRE

    Bjerke, Mia; Solaroli, Nicola; Lesko, Nicole; Balzarini, Jan; Johansson, Magnus; Karlsson, Anna

    2010-01-01

    Thymidine kinase 2 (TK2) is a mitochondrial deoxyribonucleoside kinase that phosphorylates several nucleoside analogs used in anti-viral and anti-cancer therapy. A fibroblast cell line with decreased TK2 activity was investigated in order to obtain insights in the effects of TK2 deficiency on nucleotide metabolism. The role of TK2 for the sensitivity against cytotoxic nucleoside analogs was also investigated. The TK2 deficient cells retained their sensitivity against all pyrimidine nucleoside...

  7. Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives

    Czech Academy of Sciences Publication Activity Database

    Xavier, N.M.; Goncalves-Pereira, R.; Jorda, Radek; Řezníčková, Eva; Kryštof, Vladimír; Oliveira, M.C.

    2017-01-01

    Roč. 89, č. 9 (2017), s. 1267-1281 ISSN 0033-4545 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : anticancer activity * azido nucleosides * bioactive molecules * ics-28 * N-glycosylation * nucleoside phosphoramidates * nucleoside/nucleotide analogs * Staudinger-phosphite reaction Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Organic chemistry Impact factor: 2.626, year: 2016

  8. Determination of redox potentials for the Watson-Crick base pairs, DNA nucleosides, and relevant nucleoside analogues.

    Science.gov (United States)

    Crespo-Hernandez, Carlos E; Close, David M; Gorb, Leonid; Leszczynski, Jerzy

    2007-05-17

    Redox potentials for the DNA nucleobases and nucleosides, various relevant nucleoside analogues, Watson-Crick base pairs, and seven organic dyes are presented based on DFT/B3LYP/6-31++G(d,p) and B3YLP/6-311+G(2df,p)//B3LYP/6-31+G* levels of calculations. The values are determined from an experimentally calibrated set of equations that correlate the vertical ionization (electron affinity) energy of 20 organic molecules with their experimental reversible oxidation (reduction) potential. Our results are in good agreement with those estimated experimentally for the DNA nucleosides in acetonitrile solutions (Seidel et al. J. Phys. Chem. 1996, 100, 5541). We have found that nucleosides with anti conformation exhibit lower oxidation potentials than the corresponding syn conformers. The lowering in the oxidation potential is due to the formation of an intramolecular hydrogen bonding interaction between the 5'-OH group of the sugar and the N3 of the purine bases or C2=O of the pyrimidine bases in the syn conformation. Pairing of adenine or guanine with its complementary pyrimidine base decreases its oxidation potential by 0.15 or 0.28 V, respectively. The calculated energy difference between the oxidation potential for the G.C base pair and that of the guanine base is in good agreement with the experimental value estimated recently (0.34 V: Caruso, T.; et al. J. Am. Chem. Soc. 2005, 127, 15040). The complete and consistent set of reversible redox values determined in this work for the DNA constituents is expected to be of considerable value to those studying charge and electronic energy transfer in DNA.

  9. Retained sensitivity to cytotoxic pyrimidine nucleoside analogs in thymidine kinase 2 deficient human fibroblasts.

    Science.gov (United States)

    Bjerke, Mia; Solaroli, Nicola; Lesko, Nicole; Balzarini, Jan; Johansson, Magnus; Karlsson, Anna

    2010-01-01

    Thymidine kinase 2 (TK2) is a mitochondrial deoxyribonucleoside kinase that phosphorylates several nucleoside analogs used in anti-viral and anti-cancer therapy. A fibroblast cell line with decreased TK2 activity was investigated in order to obtain insights in the effects of TK2 deficiency on nucleotide metabolism. The role of TK2 for the sensitivity against cytotoxic nucleoside analogs was also investigated. The TK2 deficient cells retained their sensitivity against all pyrimidine nucleoside analogs tested. This study suggests that nucleoside analog phosphorylation mediated by TK2 may be less important, compared to other deoxyribonucleoside kinases, for the cytotoxic effects of these compounds.

  10. Twisting and Tilting 1,1 '-Bis(dialkylphosphino)ferrocene Bound to Low Valent Tricarbonylmaganese(I to -I)

    Czech Academy of Sciences Publication Activity Database

    Schäfer, K. M.; Reinders, L.; Fiedler, Jan; Ringenberg, M. R.

    2017-01-01

    Roč. 56, č. 23 (2017), s. 14688-14696 ISSN 0020-1669 Institutional support: RVO:61388955 Keywords : 1,1´-Bis(dialkylphosphino)ferrocene DPPF * metal-metal bonds * Fe interactions Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.857, year: 2016

  11. Efficient photodegradation of Acid Red B by immobilized ferrocene in the presence of UVA and H2O2

    International Nuclear Information System (INIS)

    Nie Yulun; Hu Chun; Qu Jiuhui; Hu Xuexiang

    2008-01-01

    SiO 2 -C 2 H 4 -ferrocene (SiCFe) was synthesized by covalent grafting of ferrocene on functionalized silica gel with a -C 2 H 4 - linkage. On the basis of characterization by diffuse reflectance UV-vis spectra (DRS) and Fourier transform infrared spectra (FT-IR), ferrocene has been successfully anchored on the silica gel. Under UVA (λ max = 365 nm) irradiation, the catalyst exhibited high photocatalytic activity in the degradation of Acid Red B (ARB), especially in the presence of H 2 O 2 . Meanwhile, the catalytic activity of SiCFe was maintained effectively even after reused for 4 times without any significant destruction of ferrocene. The influence of initial solution pH and wavelength of UV light on the catalyst's activity was also investigated. Electron spin resonance (ESR) studies revealed that both ·OH and HO 2 ·/O 2 · - radicals were involved as the active species in the ARB degradation process. Furthermore, results of total organic carbon (TOC) and FT-IR analysis indicated that ARB degradation proceeded by the cleavage of -N=N-, followed by hydroxylation and opening of phenyl rings to form aliphatic acids and further oxidization of the aliphatic acids to produce carbon dioxide and water. A possible reaction mechanism was proposed on the basis of all the information obtained under various experimental conditions

  12. Purine restriction induces pronounced translational upregulation of the NT1 adenosine/pyrimidine nucleoside transporter in Leishmania major.

    Science.gov (United States)

    Ortiz, Diana; Valdés, Raquel; Sanchez, Marco A; Hayenga, Johanna; Elya, Carolyn; Detke, Siegfried; Landfear, Scott M

    2010-10-01

    Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gene resulted in pronounced upregulation of adenosine and uridine uptake mediated by the NT1 permease and also induced up to a 200-fold enhancement in the level of the NT1 protein but not mRNA. A similar level of upregulation of NT1 was achieved in wild-type promastigotes that were transferred to medium deficient in purines. Pulse labelling and treatment of cells with the translation inhibitor cycloheximide revealed that control of NT1 expression occurs primarily at the level of translation and not protein turnover. These observations imply the existence of a translational control mechanism that enhances the ability of Leishmania parasites to import essential purines when they are present at limiting concentrations. © 2010 Blackwell Publishing Ltd.

  13. Assay for inhibitors of nucleoside transport based upon the use of 5-125I]Iodo-2-deoxyuridine as permeant

    International Nuclear Information System (INIS)

    Mahony, W.B.; Zimmerman, T.P.

    1986-01-01

    5[ 125 I]Iodo-2-deoxyuridine (IdUrd) has been shown to serve as a permeant for the nucleoside transport system of human erythrocytes and to be metabolically inert in these cells. Linear initial velocities were obtained at 20 0 C for 125 IdUrd transport, yielding a K/sub m/ of 73 +/- 18 μM (n = 6). Low-affinity inhibitors of 125 IdUrd transport, such as adenosine (K/sub i/ = 32 +/- 2 μM, n = 2), could be characterized by Michaelis-Menten kinetics. However, high-affinity inhibitors, such as 6-[4-nitrobenzyl)thio]9-β-D-ribofuranosylpurine, caused nonlinear initial velocities when added to the cells simultaneously with 125 IdUrd. Conditions were defined (viz., 20-min pretreatment of cells with test compound followed by 5.0-min incubation with 1.0 μM 125 IdUrd, all at 20 0 C) whereby high-affinity inhibitors of IdUrd transport can be identified and evaluated according to their 50% inhibitory concentrations. The use of 125 IdUrd as permeant greatly expedites the testing of compounds as inhibitors of nucleoside transport by allowing the cell pellets generated in these assays to be monitored directly in a gamma spectrometer, thereby circumventing the solubilization and decolorization of cell pellets required by assays that use 3 H- or 14 C-labeled nucleoside permeants

  14. A new sensitive 32P-postlabeling assay based on the specific enzymatic conversion of bulky DNA lesions to radiolabeled dinucleotides and nucleoside 5'-monophosphates

    International Nuclear Information System (INIS)

    Randerath, Kurt; Randerath, Erika; Danna, T.F.; Van Golen, K.L.; Putman, K.L.

    1989-01-01

    A new sensitive 32 P-postlabelling assay for DNA adducts has been developed. When DNA containing bulky adducts, X 1 , X 2 , .....X n , is digested with nuclease P1 at pH 5, normal nucleotides are released as 5'-monophosphates, pN, while adducts are excised as 5'-phosphorylated dinucleotides, pX i pN, because inter-nucleotide linkages on the 3' side of X resist attack by nuclease P1. Addition of prostatic acid phosphatase to such a digest results in 5'-dephosphorylation of the nucleotides to normal nucleosides, N, and adducted dinucleotides, X i pN, carrying a 5'-terminal free hydroxyl group. The dinucleotides but not nucleosides are converted to 5'- 32 P-labeled dinucleotides,[ 32 P]pX i pN, by T4 polynucleotide kinase-catalyzed [ 32 P]posphate transfer from [γ- 32 P]ATP. Upon mapping on polyethyleneimine-cellulose anion-exchange TLC, the labeled dinucleotide adducts produce characteristic autoradiographic fingerprints. Alternatively, they are further digested with snake venom phosphodiesterase to yield 5'-monophosphates, [ 32 P]pX i and pN. TLC profiles of the monophosphate adducts are distinct from those of the dinucleotides. These reactions provide the basis of the new 32 P-postlabeling scheme, which is compared in this paper with a previously reported protocol yielding adducts in the form of 5'- 32 P-labeled 3',5'-bisphosphates, [ 32 P]pX i p. (author)

  15. Two purine nucleoside phosphorylases in Bacillus subtilis. Purification and some properties of the adenosine-specific phosphorylase

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank

    1978-01-01

    Two purine nucleoside phosphorylases (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) were purified from vegetative Bacillus subtilis cells. One enzyme, inosine-guanosine phosphorylase, showed great similarity to the homologous enzyme of Bacillus cereus. It appeared...

  16. An enzymatic glycosylation of nucleoside analogues using beta-galactosidase from Escherichia coli

    Czech Academy of Sciences Publication Activity Database

    Blažek, Jiří; Jansa, Petr; Baszczyňski, Ondřej; Kaiser, Martin Maxmilian; Otmar, Miroslav; Krečmerová, Marcela; Dračínský, Martin; Holý, Antonín; Králová, B.

    2012-01-01

    Roč. 20, č. 9 (2012), s. 3111-3118 ISSN 0968-0896 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : glycosylation * galactosylation * beta-galactosidase * enzymatic synthesis * nucleoside * acyclic nucleoside analogues Subject RIV: CC - Organic Chemistry Impact factor: 2.903, year: 2012

  17. Origin, Utilization, and Recycling of Nucleosides in the Central Nervous System

    Science.gov (United States)

    Ipata, Piero Luigi

    2011-01-01

    The brain relies on the salvage of preformed purine and pyrimidine rings, mainly in the form of nucleosides, to maintain its nucleotide pool in the proper qualitative and quantitative balance. The transport of nucleosides from blood into neurons and glia is considered to be an essential prerequisite to enter their metabolic utilization in the…

  18. Cytosine arabinoside influx and nucleoside transport sites in acute leukemia.

    Science.gov (United States)

    Wiley, J S; Jones, S P; Sawyer, W H; Paterson, A R

    1982-02-01

    Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells, since mean influxes for myeloblasts and lymphoblasts were 6- and 2.3-fold greater than polymorphs and lymphocytes, respectively. Also, the mean influx for myeloblasts was fourfold greater than the mean for lymphoblasts. The number of nucleoside transport sites was estimated for each cell type by measuring the equilibrium binding of [(3)H]nitrobenzylthioinosine (NBMPR), which inhibits nucleoside fluxes by binding with high affinity to specific sites on the transport mechanism. The mean binding site numbers for myeloblasts and lymphoblasts were 5- and 2.8-fold greater, respectively, than for the mature cells of the same maturation series. The mean number of NBMPR binding sites for myeloblasts was fourfold greater than for lymphoblasts. Patients with AUL were heterogeneous since blasts from some gave values within the myeloblastic range and others within the lymphoblastic range. The araC influx correlated closely with the number of NBMPR binding sites measured in the same cells on the same day. Transport parameters were measured on blasts from 15 patients with AML or AUL who were then treated with standard induction therapy containing araC. Eight patients entered complete remission, while seven failed therapy, among whom were the three patients with the lowest araC influx (myeloblasts have both higher araC transport rates and more nucleoside transport sites than lymphoblasts and this factor may contribute to the greater sensitivity of AML to this drug. AraC transport varied >10

  19. Addressing the selectivity and toxicity of antiviral nucleosides.

    Science.gov (United States)

    Feng, Joy Y

    2018-01-01

    Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.

  20. HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

    DEFF Research Database (Denmark)

    Vanangamudi, Murugesan; Poongavanam, Vasanthanathan; Namasivayam, Vigneshwaran

    2017-01-01

    BACKGROUND: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV-1 RT) is one of the successful chemotherapies for the treatment of HIV infection. Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown to be very promising......: The conformation dependent-alignment based (CoMFA and CoMSIA) methods have been proven very successful ligand based strategy in the drug design. Here, CoMFA and CoMSIA studies reported for structurally distinct NNRTIs including thiazolobenzimidazole, dipyridodiazepinone, 1,1,3-trioxo [1,2,4]-thiadiazine...

  1. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients

    International Nuclear Information System (INIS)

    Alangari, Abdullah; AlHarbi, Abdullah; AlGhonaium Abdulaziz; Santisteban, Ines; Hershfield, Michael

    2009-01-01

    Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT. Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly reduced, but did not completely eliminate PNP activity. (author)

  2. Emission spectroscopy of argon ferrocene mixture jet in a low pressure plasma reactor

    International Nuclear Information System (INIS)

    Tiwari, N.; Tak, A.K.; Chakravarthy, Y.; Shukla, A.; Meher, K.C.; Ghorui, S.; Thiyagarajan, T.K.

    2015-01-01

    Emission spectroscopy is employed to measure the plasma temperature and species identification in a reactor used for studying homogenous nucleation and growth of iron nano particle. Reactor employs segmented non transferred plasma torch mounted on water cooled cylindrical chamber. The plasma jet passes through graphite nozzle and expands in low pressure reactor. Ferrocene is fed into the nozzle where it mixes with Argon plasma jet. A high resolution spectrograph (SHAMROCK 303i, resolution 0.06 nm) has been used to record the spectra over a wide range. Identification of different emission lines has been done using NIST database. Lines from (700 to 860nm) were considered for calculation of temperature. Spectra were recorded for different axial location, pressure and power. Temperature was calculated using Maxwell Boltzman plot method. Variation in temperature with pressure and location is presented and possible reasons for different behaviour are explored. (author)

  3. Enantiopure Ferrocene-Based Planar-Chiral Iridacycles: Stereospecific Control of Iridium-Centred Chirality.

    Science.gov (United States)

    Arthurs, Ross A; Ismail, Muhammad; Prior, Christopher C; Oganesyan, Vasily S; Horton, Peter N; Coles, Simon J; Richards, Christopher J

    2016-02-24

    Reaction of [IrCp*Cl2 ]2 with ferrocenylimines (Fc=NAr, Ar=Ph, p-MeOC6 H4 ) results in ferrocene C-H activation and the diastereoselective synthesis of half-sandwich iridacycles of relative configuration Sp *,RIr *. Extension to (S)-2-ferrocenyl-4-(1-methylethyl)oxazoline gave highly diastereoselective control over the new elements of planar chirality and metal-based pseudo-tetrahedral chirality, to give both neutral and cationic half-sandwich iridacycles of absolute configuration Sc ,Sp ,RIr . Substitution reactions proceed with retention of configuration, with the planar chirality controlling the metal-centred chirality through an iron-iridium interaction in the coordinatively unsaturated cationic intermediate. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Electrochemical detection of carbidopa using a ferrocene-modified carbon nanotube paste electrode

    Directory of Open Access Journals (Sweden)

    FATEMEH KARIMI

    2009-12-01

    Full Text Available A chemically modified carbon paste electrode (MCPE containing ferrocene (FC and carbon nanotubes (CNT was constructed. The electrochemical behavior and stability of the MCPE were investigated by cyclic voltammetry. The electrocatalytic activity of the MCPE was investigated and it showed good characteristics for the oxidation of carbidopa (CD in phosphate buffer solution (PBS. A linear concentration range of 5 to 600 μM CD, with a detection limit of 3.6±0.17 μM CD, was obtained. The diffusion coefficient of CD and the transfer coefficient ( were also determined. The MCPE showed good reproducibility, remarkable long-term stability and especially good surface renewability by simple mechanical polishing. The results showed that this electrode could be used as an electrochemical sensor for the determination of CD in real samples, such as urine samples.

  5. Effect of ferrocene-substituted porphyrin RL-91 on Candida albicans biofilm formation.

    Science.gov (United States)

    Lippert, Rainer; Vojnovic, Sandra; Mitrovic, Aleksandra; Jux, Norbert; Ivanović-Burmazović, Ivana; Vasiljevic, Branka; Stankovic, Nada

    2014-08-01

    Ferrocene-substituted porphyrin RL-91 exhibits antifungal activity against opportune human pathogen Candida albicans. RL-91 efficiently inhibits growth of both planktonic C. albicans cells and cells within biofilms without photoactivation. The minimal inhibitory concentration for plankton form (PMIC) was established to be 100 μg/mL and the same concentration killed 80% of sessile cells in the mature biofilm (SMIC80). Furthermore PMIC of RL-91 efficiently prevents C. albicans biofilm formation. RL-91 is cytotoxic for human fibroblasts in vitro in concentration of 10 μg/mL, however it does not cause hemolysis in concentrations of up to 50 μg/mL. These findings open possibility for application of RL-91 as an antifungal agent for external antibiofilm treatment of medical devices as well as a scaffold for further development of porphyrin based systemic antifungals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Ferrocene and cobaltocene derivatives for non-aqueous redox flow batteries.

    Science.gov (United States)

    Hwang, Byunghyun; Park, Min-Sik; Kim, Ketack

    2015-01-01

    Ferrocene and cobaltocene and their derivatives are studied as new redox materials for redox flow cells. Their high reaction rates and moderate solubility are attractive properties for their use as active materials. The cyclability experiments are carried out in a static cell; the results showed that these materials exhibit stable capacity retention and predictable discharge potentials, which agree with the potential values from the cyclic voltammograms. The diffusion coefficients of these materials are 2 to 7 times higher than those of other non-aqueous materials such as vanadium acetylacetonate, iron tris(2,2'-bipyridine) complexes, and an organic benzene derivative. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

    Directory of Open Access Journals (Sweden)

    Hang Ren

    2015-12-01

    Full Text Available A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3’-fluorinated analogues were constructed from a common 3’-deoxy-3’-fluororibofuranose intermediate. Employing Suzuki and Stille cross-coupling reactions, fifteen 3’-fluororibose purine nucleosides 1–15 and eight 3’-fluororibose 2-chloro/2-aminopurine nucleosides 16–23 with various substituents at position 6 of the purine ring were efficiently synthesized. Furthermore, 3’-fluorine analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon cancer and 143B (osteosarcoma cancer tumor cell lines. We have demonstrated 3’-fluorine purine nucleoside analogues display potent tumor cell growth inhibition activity at sub- or low micromolar concentration.

  8. Selenium-Mediated Dehalogenation of Halogenated Nucleosides and its Relevance to the DNA Repair Pathway.

    Science.gov (United States)

    Mondal, Santanu; Manna, Debasish; Mugesh, Govindasamy

    2015-08-03

    Halogenated nucleosides can be incorporated into the newly synthesized DNA of replicating cells and therefore are commonly used in the detection of proliferating cells in living tissues. Dehalogenation of these modified nucleosides is one of the key pathways involved in DNA repair mediated by the uracil-DNA glycosylase. Herein, we report the first example of a selenium-mediated dehalogenation of halogenated nucleosides. We also show that the mechanism for the debromination is remarkably different from that of deiodination and that the presence of a ribose or deoxyribose moiety in the nucleosides facilitates the deiodination. The results described herein should help in understanding the metabolism of halogenated nucleosides in DNA and RNA. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. [sup 57]Fe Moessbauer spectroscopic studies of the ferrocene molecular reorientation in AlPO[sub 4]-5 and AlPO[sub 4]-8 frameworks

    Energy Technology Data Exchange (ETDEWEB)

    Lund, A.; Nicholson, D.G. (Department of Chemistry, University of Trondheim, Dragvoll (Norway)); Parish, R.V.; Wright, J.P. (Department of Chemistry, UMIST, Manchester (United Kingdom))

    1994-01-01

    [sup 57]Fe Moessbauer spectroscopic studies were carried out on ferrocene guest molecules in some microporous aluminium phosphate host lattices in order to investigate their behaviour in the aluminium phosphate channels. The 300 K spectra show broad single lines with isomer shifts of 0.39 and 0.41 mm s[sup -1] relative to iron for AlPO[sub 4]-5:ferrocene and AlPO[sub 4]-8:ferrocene inclusion compounds, respectively. The absence of quadrupole splittings for these materials contrasts with the large quadrupole splitting observed for ferrocene itself at the same temperature. The low-temperature spectrum (20 K) for AlPO[sub 4]-5:ferrocene shows a doublet with quadrupole splitting of 2.37 mm s[sup -1] and an isomer shift of 0.55 mm s[sup -1]. The collapse of the quadrupole splitting at room temperature is consistent with the ferrocene molecules rotating within the channels. (au).

  10. Alkylsulfanylphenyl derivatives of cytosine and 7-deazaadenine nucleosides, nucleotides and nucleoside triphosphates. Synthesis, polymerase incorporation to DNA and electrochemical study

    Czech Academy of Sciences Publication Activity Database

    Macíčková-Cahová, Hana; Pohl, Radek; Horáková Brázdilová, Petra; Havran, Luděk; Špaček, Jan; Fojta, Miroslav; Hocek, Michal

    2011-01-01

    Roč. 17, č. 21 (2011), s. 5833-5841 ISSN 0947-6539 R&D Projects: GA MŠk(CZ) LC06035; GA MŠk LC512; GA ČR GA203/09/0317; GA AV ČR(CZ) IAA400040901 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : DNA polymerases * electrochemistry * nucleosides * nucleotides * organosulfur compounds Subject RIV: CC - Organic Chemistry Impact factor: 5.925, year: 2011

  11. Do non-nucleoside reverse transcriptase inhibitors contribute to lipodystrophy?

    Science.gov (United States)

    Nolan, David

    2005-01-01

    Lipodystrophy complications, including lipoatrophy (pathological fat loss) and metabolic complications, have emerged as important long-term toxicities associated with antiretroviral therapy in the current era. The wealth of data that has accumulated over the past 6 years has now clarified the contribution of specific antiretroviral drugs to the risk of these clinical endpoints, with evidence that lipoatrophy is strongly associated with the choice of nucleoside reverse transcriptase inhibitor therapy (specifically, stavudine and to a lesser extent zidovudine). The aetiological basis of metabolic complications of antiretroviral therapy has proven to be complex, in that the risk appears to be modulated by a number of lifestyle factors that have made the metabolic syndrome highly prevalent in the general population, with additional contributions from HIV disease status itself, as well as from individual drugs within the HIV protease inhibitor class. The currently licensed non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs, efavirenz and nevirapine, have been proven to have a favourable safety profile in terms of lipodystrophy complications. However, it must be noted that NNRTI drugs also have individual toxicity profiles that must be accounted for when considering and/or monitoring their use in the treatment of HIV infection.

  12. Nucleobases, nucleosides, and nucleotides: versatile biomolecules for generating functional nanomaterials.

    Science.gov (United States)

    Pu, Fang; Ren, Jinsong; Qu, Xiaogang

    2018-02-21

    The incorporation of biomolecules into nanomaterials generates functional nanosystems with novel and advanced properties, presenting great potential for applications in various fields. Nucleobases, nucleosides and nucleotides, as building blocks of nucleic acids and biological coenzymes, constitute necessary components of the foundation of life. In recent years, as versatile biomolecules for the construction or regulation of functional nanomaterials, they have stimulated interest in researchers, due to their unique properties such as structural diversity, multiplex binding sites, self-assembly ability, stability, biocompatibility, and chirality. In this review, strategies for the synthesis of nanomaterials and the regulation of their morphologies and functions using nucleobases, nucleosides, and nucleotides as building blocks, templates or modulators are summarized alongside selected applications. The diverse applications range from sensing, bioimaging, and drug delivery to mimicking light-harvesting antenna, the construction of logic gates, and beyond. Furthermore, some perspectives and challenges in this emerging field are proposed. This review is directed toward the broader scientific community interested in biomolecule-based functional nanomaterials.

  13. Labeling and biological Characterization of an antibiotic for infection detection

    International Nuclear Information System (INIS)

    Essouiss, Imen; Ghali, Wafa; Saied, Nadia; Saidi, M.

    2009-01-01

    Nuclear imaging is a non-invasive exploration technique, used for rapid diagnostic of infectious disease Thus, for osteoarticular infection scintigraphic techniques were proposed to ameliorate the diagnostic sensibility and the use of radiolabeled antibiotics as imaging agents of infectious loci become more and more recognized. In this work, a new sulfanilamid derivative, the N-sulfanilamide-ferrocene-carboxamide was chemically synthesized then labeled with technetium-99m, with a radiochemical yield, 82 pourcent In in-vitro studies were done with E.coli. first , the up-take of labeled molecule was estimated as 65 pourcent. Then, the bacteriostatical effect of the molecule was determinated by considering the Optical Density at 600 nm. The obtained results, encourage us to do more, with biodistibution on normal and infected mice ; with staphylococcus aureus. Then to carry out scintigraphic imaging with gamma camera to check out the potentiality of the molecule as an infectious imaging agent

  14. Observation of the Strong Electronic Coupling in Near-Infrared-Absorbing Tetraferrocene aza-Dipyrromethene and aza-BODIPY with Direct Ferrocene-α- and Ferrocene-β-Pyrrole Bonds: Toward Molecular Machinery with Four-Bit Information Storage Capacity.

    Science.gov (United States)

    Zatsikha, Yuriy V; Holstrom, Cole D; Chanawanno, Kullapa; Osinski, Allen J; Ziegler, Christopher J; Nemykin, Victor N

    2017-01-17

    The 1,3,7,9-tetraferrocenylazadipyrromethene (3) and the corresponding 1,3,5,7-tetraferrocene aza-BODIPY (4) were prepared via three and four synthetic steps, respectively, starting from ferrocenecarbaldehyde using the chalcone-type synthetic methodology. The novel tetra-iron compounds have ferrocene groups directly attached to both the α- and the β-pyrrolic positions, and the shortest Fe-Fe distance determined by X-ray crystallography for 3 was found to be ∼6.98 Å. These new compounds were characterized by UV-vis, nuclear magnetic resonance, and high-resolution electrospray ionization mass spectrometry methods, while metal-metal couplings in these systems were probed by electro- and spectroelectrochemistry, chemical oxidations, and Mössbauer spectroscopy. Electrochemical data are suggestive of the well-separated stepwise oxidations of all four ferrocene groups in 3 and 4, while spectroelectrochemical and chemical oxidation experiments allowed for characterization of the mixed-valence forms in the target compounds. Intervalence charge-transfer band analyses indicate that the mixed-valence [3] + and [4] + complexes belong to the weakly coupled class II systems in the Robin-Day classification. This interpretation was further supported by Mössbauer spectroscopy in which two individual doublets for Fe(II) and Fe(III) centers were observed in room-temperature experiments for the mixed-valence [3] n+ and [4] n+ species (n = 1-3). The electronic structure, redox properties, and UV-vis spectra of new systems were correlated with Density Functional Theory (DFT) and time-dependent DFT calculations (TDDFT), which are suggestive of a ferrocene-centered highest occupied molecular orbital and chromophore-centered lowest unoccupied molecular orbital in 3 and 4 as well as predominant spin localization at the ferrocene fragment attached to the α-pyrrolic positions in [3] + and [4] + .

  15. Electrochemical Studies of Interactions Between Fe(II/Fe(III and Amino Acids Using Ferrocene-Modified Carbon Paste Electrode

    Directory of Open Access Journals (Sweden)

    Vatrál Jaroslav

    2014-12-01

    Full Text Available The electrochemical behavior of an Fe(II/Fe(III redox couple in the presence of various selected amino acids has been studied using ferrocene-modified carbon paste electrode at pH = 7.4. Because of Fe(II/Fe(III solubility issues at physiological pH, ferrocene was used as a source of iron. Anodic oxidation of iron (pH = 7.2 occurred at 0.356 V and cathodic oxidation at 0.231 V, both vs Ag|AgCl. Treatment of the voltammetric data showed that it was a purely diffusion-controlled reaction with the involvement of one electron. After addition of amino acids, potential shifts and current changes can be observed on the voltammograms. Cyclic voltammetry experiments revealed the capability of amino acids to change the electrochemical behavior of the Fe(II/Fe(III redox couple.

  16. Solvent Effects in the Electroreduction of Ferrocene at Pt in the Temperature Range 200-300 K

    Science.gov (United States)

    1991-03-20

    been obtained at iow temperatures downto 92 K ata P ulramcroeectode(dimete, 2 pm inthree alcohol solvents, namely, methanol, ethanol , and n-propanol. In...In this aree.-doutee-eace&4 Kinetic parameters for the electrooxidation of ferrocene have been obtained at low temperatures down to 193 ’K at a Pt...with solvent nature. tnsvetsiky of~aitm Davis, CA 95616 Kinetic data obtained in mteehanol, ethanol . and I1- propanol as a function of temperature

  17. The preparation of 3-H-labeled Acyclic Nucleoside Phosphonates and Study of their Stability

    Czech Academy of Sciences Publication Activity Database

    Elbert, Tomáš; Břehová, Petra; Holý, Antonín

    2010-01-01

    Roč. 75, č. 7 (2010), s. 757-766 ISSN 0010-0765 R&D Projects: GA MŠk 1M0508; GA AV ČR IAA400550801 Institutional research plan: CEZ:AV0Z40550506 Keywords : tritium * 3-H NMR * acyclic nucleotide analogues Subject RIV: CC - Organic Chemistry Impact factor: 0.853, year: 2010

  18. Nucleoside-metallacarborane conjugates for base-specific metal labeling of DNA

    Czech Academy of Sciences Publication Activity Database

    Olejniczak, A. B.; Plešek, Jaromír; Lesnikowski, Z. J.

    2007-01-01

    Roč. 13, č. 1 (2007), s. 311-318 ISSN 0947-6539 Grant - others:KBN(PL) PBZ-KBN-059/T09/081 Institutional research plan: CEZ:AV0Z40320502 Keywords : alkylation * bioinorganic chemistry * metallacarboranes Subject RIV: CA - Inorganic Chemistry Impact factor: 5.330, year: 2007

  19. Anion-exchange analysis of isotopically labelled nucleotides, nucleosides, and bases in metabolic disorders

    International Nuclear Information System (INIS)

    Nissinen, E.A.O.

    1987-01-01

    This paper on the importance of cellular purines and pyrimidines is evidenced by the multitude of diseases, such as hyperuricemia, orotic aciduria, gout, Lesch-Nyhan syndrome, immunodeficiencies with B- and T-cell dysfunctions, etc. which result from aberrant metabolism. In addition, the use of purine and pyrimidine analogs in chemotherapy is of growing interest. Purine metabolism consists of a complex network of biochemical pathway. These pathways are under complicated feedback regulation and there also exists a close relationship between purine and pyrimidine metabolism. In addition, these pathways interact with those of the carbohydrate, amino acid, and energy metabolism. Since metabolic pathways are closely interrelated, a change in the concentration of a particular metabolite may lead to many changes in the overall metabolic profiles. For instance, in the area of nucleotide metabolism, the inhibition of IMP dehydrogenase by mycophenolic acid leads to various changes in both purine and pyrimidine nucleotide pools. Inhibition of de nova purine biosynthesis by methotrexate leads to many changes in purine and pyrimidine ribonucleotides and deoxyribonucleotides. Thus, the simultaneous measurement of all cellular purine and pyrimidine metabolites from individuals whose metabolism is altered, either by a metabolic disease or by the action of drugs, may further our understanding of cellular metabolism

  20. Phenothiazine-linked nucleosides and nucleotides for redox labelling of DNA

    Czech Academy of Sciences Publication Activity Database

    Simonova, Anna; Havran, Luděk; Pohl, Radek; Fojta, Miroslav; Hocek, Michal

    2017-01-01

    Roč. 15, č. 33 (2017), s. 6984-6996 ISSN 1477-0520 R&D Projects: GA ČR GBP206/12/G151 Grant - others:AV ČR(CZ) AP1501; AV ČR(CZ) AP1501 Program:Akademická prémie - Praemium Academiae; Akademická prémie - Praemium Academiae Institutional support: RVO:61388963 ; RVO:68081707 Keywords : electrochemical detection * primer extension * 2'-deoxyribonucleoside triphosphates Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.564, year: 2016 http://pubs.rsc.org/en/content/articlehtml/2017/ob/c7ob01439b

  1. Triazole nucleoside derivatives bearing aryl functionalities on the nucleobases show antiviral and anticancer activity.

    Science.gov (United States)

    Xia, Yi; Qu, Fanqi; Peng, Ling

    2010-08-01

    Synthetic nucleoside mimics are important candidates in the searing for antiviral and anticancer drugs. Ribavirin, the first antiviral nucleoside drug, is unique in its antiviral activity with mutilple modes of action, which are mainly due to its special triazole heterocycle as nucleobase. Additionally, introducing aromatic functionalities to the nucleobase is able to confer novel mechanisms of action for nucleoside mimics. With the aim to combine the special characteristics of unnatural triazole heterocycles with those of the appended aromatic groups on the nucleobases, novel 1,2,4-triazole nucleoside analogs bearing aromatic moieties were designed and developed. The present short review summarizes the molecular design, chemical synthesis and biological activity of these triazole nucleoside analogs. Indeed, the discovery of antiviral and anticancer activities shown by these triazole nucleosides as well as the new mechanism underlying the biological activity by one of the anticancer leads has validated the rationale for molecular design and impacted us to further explore the concept with the aim of developing structurally novel nucleoside drug candidates with new modes of action.

  2. Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

    Science.gov (United States)

    Liu, Zhi-Qiang; Zhang, Bo; Lin, Shan; Baker, Peter James; Chen, Mao-Sheng; Xue, Ya-Ping; Wu, Hui; Xu, Feng; Yuan, Shui-Jin; Teng, Yi; Wu, Ling-Fang

    2017-01-01

    To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis. PMID:29333435

  3. Addition of ferrocene controls polymorphism and enhances charge mobilities in poly(3-hexylthiophene) thin-film transistors

    Science.gov (United States)

    Smith, Brandon; Clark, Michael; Grieco, Christopher; Larsen, Alec; Asbury, John; Gomez, Enrique

    2015-03-01

    Crystalline organic molecules often exhibit the ability to form multiple crystal structures depending on the processing conditions. Exploiting this polymorphism to optimize molecular orbital overlap between adjacent molecules within the unit lattice of conjugated polymers is an approach to enhance charge transport within the material. We have demonstrated the formation of tighter π- π stacking poly(3-hexylthiophene-2,5-diyl) polymorphs in films spin coated from ferrocene-containing solutions using grazing incident X-ray diffraction. As a result, we found that the addition of ferrocene to casting solutions yields thin-film transistors which exhibit significantly higher source-drain current and charge mobilities than neat polymer devices. Insights gleaned from ferrocene/poly(3-hexylthiophene) mixtures can serve as a template for selection and optimization of next generation small molecule/polymer systems possessing greater baseline charge mobilities. Ultimately, the development of such techniques to enhance the characteristics of organic transistors without imparting high costs or loss of advantageous properties will be a critical factor determining the future of organic components within the electronics market.

  4. Aqueous microwaves assisted cross-coupling reactions applied to unprotected nucleosides.

    Directory of Open Access Journals (Sweden)

    CHRISTOPHE eLEN

    2015-02-01

    Full Text Available Nucleoside analogues have attracted much attention due to their potential biological activities. Amongst all synthetic nucleosides, C5-modified pyrimidines and C7- or C8-modified purines have mostly been prepared using palladium cross-coupling reactions and then studied as antitumoral and antiviral agents. Our objective is to focus this review on the Suzuki-Miyaura and on the Heck cross-couplings of nucleosides using microwave irradiations which are an alternative technology compatible with green chemistry and sustainable development.

  5. Nutrition Labeling

    DEFF Research Database (Denmark)

    Grunert, Klaus G

    2013-01-01

    because consumers will avoid products that the label shows to be nutritionally deficient, but also because food producers will try to avoid marketing products that appear, according to the label, as nutritionally problematic, for example, because of a high content of saturated fat or salt. Nutrition......Nutrition labeling refers to the provision of information on a food product’s nutritional content on the package label. It can serve both public health and commercial purposes. From a public health perspective, the aim of nutrition labeling is to provide information that can enable consumers...... to make healthier choices when choosing food products. Nutrition labeling is thus closely linked to the notion of the informed consumer, that chooses products according to their aims, on the basis of the information at their disposal. Because many consumers are assumed to be interested in making healthy...

  6. Private Labels

    OpenAIRE

    Kolmačková, Zuzana

    2013-01-01

    This Bachelor Thesis titled Private labels deals with distribution strategy based on the introduction of private labels especially in retail chains. At the beginning it is focused on the general concept of private label offered by retailers, where is mentioned basic characteristics, history and structuring of distribution brands. Subsequently this thesis informs readers about the introduction of new special distribution brands, which focus primarily on the new consumption habits of customers....

  7. Substrate coated with receptor and labelled ligand for assays

    International Nuclear Information System (INIS)

    1980-01-01

    Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

  8. Modification of Purine and Pyrimidine Nucleosides by Direct C-H Bond Activation

    Directory of Open Access Journals (Sweden)

    Yong Liang

    2015-03-01

    Full Text Available Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized via direct activation of the C8-H bond in purine and the C5-H or C6-H bond in uracil bases. The review focuses on Pd/Cu-catalyzed couplings between unactivated nucleoside bases with aryl halides. It also discusses cross-dehydrogenative arylations and alkenylations as well as other reactions used for modification of nucleoside bases that avoid the use of organometallic precursors and involve direct C-H bond activation in at least one substrate. The scope and efficiency of these coupling reactions along with some mechanistic considerations are discussed.

  9. Molecular moment similarity between several nucleoside analogs of thymidine and thymidine. sil@watson.ibm.com.

    Science.gov (United States)

    Silverman, B D; Pitman, M C; Platt, D E

    1999-06-01

    Molecular moment descriptors of the shape and charge distributions of twenty five nucleoside structures have been examined. The structures include thymidine as well as the difluorotoluene nucleoside analog which has been found to pair efficiently with adenine by polymerase catalysis. The remaining twenty three structures have been chosen to be as structurally similar to thymidine and to the difluorotoluene nucleoside analog as possible. The moment descriptors which include a description of the relationship of molecular charge to shape show the difluorotoluene nucleoside to be one of the most proximate molecules to thymidine in the space of the molecular moments. The calculations, therefore, suggest that polymerase specificity might be not only a consequence of molecular steric features alone but also of the molecular electrostatic environment and its registration with molecular shape.

  10. Sustainability Labeling

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    Sustainability labeling originated from a need to protect the identity of alternative systems of food production and to increase market transparency. From the 1980s onwards sustainability labeling has changed into a policy instrument replacing direct government regulation of the food market, and a

  11. Effect of iron on the production of high electrocatalytic activity carbons from ferrocene - PFA mixtures

    International Nuclear Information System (INIS)

    Cashion, J.D.; Brown, L.J.; Ozaki, J.; Yamada, K.; Nozawa, K.; Matsui, K.; Oya, A.

    1999-01-01

    Full text: We have previously studied the carbonisation of mixtures of ferrocene and poly(furfury 1 alcohol) (PFA) which, after heating at 700 deg C, produces electrodes with an electrocatalytic activity comparable to that of platinum. The carbons have a distinctive furry structure under the SEM and an XRD profile characteristic of turbostratic carbon. The iron had been converted to a mixture of α- and γiron and cementite, Fe 3 C and we conjectured that the furry carbon could be formed by the exsolution of carbon from the γ iron on cooling. The present experiments have shown that changing the cooling rate has only a small effect so exsolution is not the cause. However, the increased conductivity correlates well with the proportion of turbostratic carbon which, in turn, correlates with the percentage of cementite. The turbostratic carbon forms cages surrounding an iron phase, presumably the cementite. The conductivity data can be fitted well to either a power law or logarithmic behaviour above the percolation theory critical concentration. The normal percolation theory model for conductivity assumes a growing volume of good conductor in an insulating matrix. However, our system has a good conductor in a matrix of moderate conductor, the conductivity of which is not constant but is increasing under heat treatment at the same time as the good conductor volume is increasing. Some possible analyses will be given

  12. Graphene by one-step chemical vapor deposition from ferrocene vapors: Properties and electrochemical evaluation

    Science.gov (United States)

    Pilatos, George; Perdikaki, Anna V.; Sapalidis, Andreas; Pappas, George S.; Giannakopoulou, Tatiana; Tsoutsou, Dimitra; Xenogiannopoulou, Evangelia; Boukos, Nikos; Dimoulas, Athanasios; Trapalis, Christos; Kanellopoulos, Nick K.; Karanikolos, Georgios N.

    2016-02-01

    Growth of few-layer graphene using ferrocene as precursor by chemical vapor deposition is reported. The growth did not involve any additional carbon or catalyst source or external hydrocarbon gases. Parametric investigation was performed using different conditions, namely, varying growth temperature from 600 to1000 °C, and growth duration from 5 min to 3 h, as well as using fast quenching or gradual cooling after the thermal treatment, in order to examine the effect on the quality of the produced graphene. The growth took place on silicon wafers and resulted, under optimal conditions, in formation of graphene with 2-3 layers and high graphitic quality, as evidenced by Raman spectroscopy, with characteristic full width at half maximum of the 2D band of 49.46 cm-1, and I2D/IG and ID/IG intensity ratios of 1.15 and 0.26, respectively. Atomic force microscopy and X-ray photoelectron spectroscopy were employed to further evaluate graphene characteristics and enlighten growth mechanism. Electrochemical evaluation of the developed material was performed using cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic charge-discharge measurements.

  13. Synthesis and in vacuo deposition of iron oxide nanoparticles by microplasma-assisted decomposition of ferrocene

    International Nuclear Information System (INIS)

    Schaefer, Michael; Kumar, Ajay; Mohan Sankaran, R.; Schlaf, Rudy

    2014-01-01

    Microplasma-assisted gas-phase nucleation has emerged as an important new approach to produce high-purity, nanometer-sized, and narrowly dispersed particles. This study aims to integrate this technique with vacuum conditions to enable synthesis and deposition in an ultrahigh vacuum compatible environment. The ultimate goal is to combine nanoparticle synthesis with photoemission spectroscopy-based electronic structure analysis. Such measurements require in vacuo deposition to prevent surface contamination from sample transfer, which can be deleterious for nanoscale materials. A homebuilt microplasma reactor was integrated into an existing atomic layer deposition system attached to a surface science multi-chamber system equipped with photoemission spectroscopy. As proof-of-concept, we studied the decomposition of ferrocene vapor in the microplasma to synthesize iron oxide nanoparticles. The injection parameters were optimized to achieve complete precursor decomposition under vacuum conditions, and nanoparticles were successfully deposited. The stoichiometry of the deposited samples was characterized in situ using X-ray photoelectron spectroscopy indicating that iron oxide was formed. Additional transmission electron spectroscopy characterization allowed the determination of the size, shape, and crystal lattice of the particles, confirming their structural properties.

  14. Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

    Directory of Open Access Journals (Sweden)

    Leonie Harmse

    Full Text Available Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05. Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05, with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

  15. Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

    Science.gov (United States)

    Harmse, Leonie; Dahan-Farkas, Nurit; Panayides, Jenny-Lee; van Otterlo, Willem; Penny, Clement

    2015-01-01

    Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05). Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05), with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

  16. Inhibition by nucleosides of glucose-transport activity in human erythrocytes.

    OpenAIRE

    Jarvis, S M

    1988-01-01

    The interaction of nucleosides with the glucose carrier of human erythrocytes was examined by studying the effect of nucleosides on reversible cytochalasin B-binding activity and glucose transport. Adenosine, inosine and thymidine were more potent inhibitors of cytochalasin B binding to human erythrocyte membranes than was D-glucose [IC50 (concentration causing 50% inhibition) values of 10, 24, 28 and 38 mM respectively]. Moreover, low concentrations of thymidine and adenosine inhibited D-glu...

  17. Lipases in green chemistry: acylation and alcoholysis on steroids and nucleosides.

    Science.gov (United States)

    Baldessari, Alicia; Iglesias, Luis E

    2012-01-01

    In this article, we describe the application of lipases in acylation and alcoholysis reactions on steroids and nucleosides. In the field of steroids, a variety of acetyl and fatty acid derivatives of androstanes, pregnanes, and cholestanes have been prepared through lipase-catalyzed acylation and alcoholysis reactions taking advantage of the high regio- and stereoselectivity of these enzymes. The substrates as well as the products show a high degree of biological activity as neurosteroids, hormones, and glucocorticoids. The regioselective preparation of diacylated nucleosides by means of an enzymatic alcoholysis allowed the synthesis of nucleosides prodrugs or modified nucleosides. The quantitative full deacylation and dealkoxycarbonylation of nucleosides and steroids is a mild synthetic method for the deprotection of these labile compounds. Some of the reported steroid and nucleoside products are novel, and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. The advantages presented by this methodology, such as selectivity, mild reaction conditions, and low environmental impact, make the lipases an important tool in the application of the principles of Green Chemistry, offering a convenient way to prepare derivatives of natural compounds with a great potential in the pharmaceutical industry.

  18. HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial.

    Science.gov (United States)

    Tashima, Karen T; Smeaton, Laura M; Fichtenbaum, Carl J; Andrade, Adriana; Eron, Joseph J; Gandhi, Rajesh T; Johnson, Victoria A; Klingman, Karin L; Ritz, Justin; Hodder, Sally; Santana, Jorge L; Wilkin, Timothy; Haubrich, Richard H

    2015-12-15

    Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials. To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents. Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394). Outpatient HIV clinics. Treatment-experienced patients with HIV infection and viral resistance. Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs. The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment. 360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group. Unblinded study design, and the study may not be applicable to resource-poor settings. Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population. National Institute of Allergy and Infectious Diseases, Boehringer Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram Biosciences (LabCorp).

  19. Unusual metal-ligand charge transfer in ferrocene functionalized μ{sub 3}-O iron carboxylates observed with Mössbauer spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Mereacre, Valeriu, E-mail: valeriu.mereacre@kit.edu [Institut für Anorganische Chemie, Karlsruher Institut für Technologie, D-76131 Karlsruhe (Germany); Schlageter, Martin; Eichhöfer, Andreas [Institut für Nanotechnologie, Karlsruher Institut für Technologie, D-76344 Eggenstein-Leopoldshafen (Germany); Bauer, Thomas; Wolny, Juliusz A.; Schünemann, Volker [Department of Physics, University of Kaiserslautern, D-67663 Kaiserslautern (Germany); Powell, Annie K., E-mail: annie.powell@kit.edu [Institut für Anorganische Chemie, Karlsruher Institut für Technologie, D-76131 Karlsruhe (Germany); Institut für Nanotechnologie, Karlsruher Institut für Technologie, D-76344 Eggenstein-Leopoldshafen (Germany)

    2016-06-01

    Temperature dependent Mössbauer studies of two ferrocenecarboxylate functionalized {Fe_3O} complexes in solid state are reported. It was found that conjugation of ferrocene ring orbitals with the π orbitals of the adjacent carboxylic group promotes a shift of electron density from the ferrocene Fe{sup II} ion to the cyclopentadienide rings with π-orbital character giving rise to a new type of mixed-valence compound. - Highlights: • In this manuscript we describe a mechanism of electron density shift which stabilizes the trapped mixed-valence state. • The coexistence of ferrocene and ferrocenium in solid state was determined. • A mixed-valence state at room-temperature and a thermally induced electron transfer with gradual interconversion were observed.

  20. Loading of Two Related Metal-Organic Frameworks (MOFs, [Cu2(bdc2(dabco] and [Cu2(ndc2(dabco], with Ferrocene

    Directory of Open Access Journals (Sweden)

    Wolfgang Wenzel

    2011-09-01

    Full Text Available We have studied the loading of two related, similar porous metal-organic frameworks (MOFs [Cu2(bdc2(dabco] (1, and [Cu2(ndc2(dabco] (2 with ferrocene by exposing bulk powder samples to the corresponding vapor. On the basis of powder X-ray diffraction data and molecular dynamics (MD calculations we propose that each pore can store one ferrocene molecule. Despite the rather pronounced similarity of the two MOFs a quite different behavior is observed, for 1 loading with ferrocene leads to an anisotropic 1% contraction, whereas for 2 no deformation is observed. Mössbauer spectroscopy studies reveal that the Fe oxidation level remains unchanged during the process. Time dependent studies reveal that the diffusion constant governing the loading from the gas-phase for 1 is approximately three times larger than the value for 2.

  1. The mechanism of mediated oxidation of carboxylates with ferrocene as redox catalyst in absence of grafting effects. An experimental and theoretical approach

    International Nuclear Information System (INIS)

    Hernández-Muñoz, Lindsay S.; Galano, Annia; Astudillo-Sánchez, Pablo D.; Abu-Omar, Mahdi M.; González, Felipe J.

    2014-01-01

    Graphical abstract: - Highlights: • The mechanism of mediated oxidation of carboxylates. • Thermodynamics of the mediated Kolbe and Non-Kolbe mechanisms. • The oxidation of acetate and diphenylacetate ions by using ferrocene as redox catalyst. • Simulation and DFT calculations of the mediated oxidation of carboxylates. • Radical and carbocationic pathways in the carboxylate oxidation in acetonitrile. - Abstract: The oxidation of tetrabutylammonium carboxylates by using ferrocene derivatives as redox mediators has been recently used to perform the covalent grafting of carbon surfaces with organic and organometallic groups. Due to the intervention of this surface process, a partial description of the reaction mechanism has only been stated. Therefore, this article concerns about two features of the oxidation of carboxylates mediated by ferrocene. In the first part, it is discussed that in the oxidation of acetate ions by using ferrocene as redox catalyst, the gap between both oxidation potentials is very high, which means that the homogeneous electron transfer between the acetate ion and the electrochemically generated ferrocenium ion is energetically unfavorable. However, by using density functional theory calculations, it has been shown that the whole set of coupled chemical reactions involved either in a Kolbe or Non-Kolbe pathway drive the overall mechanisms towards a thermodynamically favorable situation. In order to avoid the strong covalent grafting process that occurs during the mediated oxidation of acetate ions, the second part of this work deals with the oxidation of tetrabutylammonium diphenylacetate by using ferrocene as a redox mediator in acetonitrile on glassy carbon electrodes. With this carboxylate, no electrode inhibition process occurs and, therefore cyclic voltammetry simulation was done to propose the electrochemical and chemical steps that are present when a carboxylate oxidation is performed in the presence of ferrocene derivatives

  2. Characterization of reactive intermediates in laser photolysis of nucleoside using of sodium salt anthraquinone-2-sulfonic acid as photosensitizer

    International Nuclear Information System (INIS)

    Ma Jianhua; Lin Weizhen; Wang Wenfeng; Han Zhenhui; Yao Side; Lin Nianyun

    1999-01-01

    The interaction of triplet state of sodium salt of anthraquinone-2-sulfonic acid (AQS) with nucleosides has been investigated in CH 3 CN using KrF(248 nm) laser flash photolysis. The transient absorption spectra and kinetics obtained from the interaction of triplet AQS and nucleoside demonstrated that the primary ionic radical pair, radical cation of nucleosides and radical anion of AQS has been detected simultaneously for the first time

  3. Pesticide Labels

    Science.gov (United States)

    Pesticide labels translate results of our extensive evaluations of pesticide products into conditions, directions and precautions that define parameters for use of a pesticide with the goal of ensuring protection of human health and the environment.

  4. A Ferrocene-Quinoxaline Derivative as a Highly Selective Probe for Colorimetric and Redox Sensing of Toxic Mercury(II Cations

    Directory of Open Access Journals (Sweden)

    Antonio Caballero

    2010-12-01

    Full Text Available A new chemosensor molecule 3 based on a ferrocene-quinoxaline dyad recognizes mercury (II cations in acetonitrile solution. Upon recognition, an anodic shift of the ferrocene/ferrocenium oxidation peaks and a progressive red-shift (Δλ = 140 nm of the low-energy band, are observed in its absorption spectrum. This change in the absorption spectrum is accompanied by a colour change from orange to deep green, which can be used for a “naked-eye” detection of this metal cation.

  5. Labelling patients

    International Nuclear Information System (INIS)

    Strudwick, R.M.

    2016-01-01

    This article looks at how diagnostic radiographers label their patients. An ethnographic study of the workplace culture in one diagnostic imaging department was undertaken using participant observation for four months and semi-structured interviews with ten key informants. One of the key themes; the way in which radiographers label their patients, is explored in this article. It was found from the study that within the department studied the diagnostic radiographers labelled or categorised their patients based on the information that they had. This information is used to form judgements and these judgements were used to assist the radiographers in dealing with the many different people that they encountered in their work. This categorisation and labelling of the patient appears to assist the radiographer in their decision-making processes about the examination to be carried out and the patient they are to image. This is an important aspect of the role of the diagnostic radiographer. - Highlights: • I have studied the culture in one imaging department. • Radiographers label or categorise their patients. • These labels/categories are used to manage the patient. • This is an important aspect of the way in which radiographers work.

  6. Profiling of modified nucleosides from ribonucleic acid digestion by supercritical fluid chromatography coupled to high resolution mass spectrometry.

    Science.gov (United States)

    Laboureur, Laurent; Guérineau, Vincent; Auxilien, Sylvie; Yoshizawa, Satoko; Touboul, David

    2018-02-16

    A method based on supercritical fluid chromatography coupled to high resolution mass spectrometry for the profiling of canonical and modified nucleosides was optimized, and compared to classical reverse-phase liquid chromatography in terms of separation, number of detected modified nucleosides and sensitivity. Limits of detection and quantification were measured using statistical method and quantifications of twelve nucleosides of a tRNA digest from E. coli are in good agreement with previously reported data. Results highlight the complementarity of both separation techniques to cover the largest view of nucleoside modifications for forthcoming epigenetic studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Rilpivirine: a new non-nucleoside reverse transcriptase inhibitor.

    Science.gov (United States)

    Sharma, Mamta; Saravolatz, Louis D

    2013-02-01

    Rilpivirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that is approved for HIV-1 treatment-naive adult patients in combination with other antiretroviral agents. The recommended dose is a 25 mg tablet once daily taken orally with a meal. Due to cytochrome P450 3A4 enzyme induction or gastric pH increase, rilpivirine cannot be coadministered with a number of other drugs (anticonvulsants, rifabutin, rifampicin, rifapentine, proton pump inhibitors, systemic dexamethasone and St John's wort). Rilpivirine should be used with caution when coadministered with a drug with a known risk for torsade de pointes. Rilpivirine has a better tolerability than a comparative NNRTI, efavirenz, in clinical trials, with fewer central nervous system adverse effects, rashes, lipid abnormalities and discontinuation rates. Virological failure occurs more commonly with higher baseline viral loads (>100,000 copies/mL) and lower baseline CD4 counts (<50 cells/mm(3)). Seventeen NNRTI mutations have been associated with decreased susceptibility to rilpivirine: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C, M230I/L, Y188L and the combination L100I + K103N. Resistance to rilpivirine largely excludes future use of the NNRTI class.

  8. Visualizing multistep elevator-like transitions of a nucleoside transporter.

    Science.gov (United States)

    Hirschi, Marscha; Johnson, Zachary Lee; Lee, Seok-Yong

    2017-05-04

    Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain moves a large distance across the membrane. This mechanism has been characterized by a transition between two states, but the conformational path that leads to the transition is not yet known, largely because the available structural information has been limited to the two end states. Here we present crystal structures of the inward-facing, intermediate, and outward-facing states of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we determined the structures of multiple intermediate conformations, in which the transport domain is captured halfway through its elevator motion. Our structures present a trajectory of the conformational transition in the elevator model, revealing multiple intermediate steps and state-dependent conformational changes within the transport domain that are associated with the elevator-like motion.

  9. Oxidation of pyrimidine nucleosides and nucleotides by osmium tetroxide.

    Science.gov (United States)

    Burton, K

    1967-08-01

    1. Pyrimidine nucleosides such as thymidine, uridine or cytidine are oxidized readily at 0 degrees by osmium tetroxide in ammonium chloride buffer. There is virtually no oxidation in bicarbonate buffer of similar pH. Oxidation of 1-methyluracil yields 5,6-dihydro-4,5,6-trihydroxy-1-methyl-2-pyrimidone. 2. Osmium tetroxide and ammonia react reversibly in aqueous solution to form a yellow 1:1 complex, probably OsO(3)NH. A second molecule of ammonia must be involved in the oxidation of UMP since the rate of this reaction is approximately proportional to the square of the concentration of unprotonated ammonia. 3. 4-Thiouridine reacts with osmium tetroxide much more rapidly than does uridine. The changes of absorption spectra are different in sodium bicarbonate buffer and in ammonium chloride buffer. They occur faster in the latter buffer and, under suitable conditions, cytidine is a major product. 4. Polyuridylic acid is oxidized readily by ammoniacal osmium tetroxide, but its oxidation is inhibited by polyadenylic acid. Pyrimidines of yeast amino acid-transfer RNA are oxidized more slowly than the corresponding mononucleosides, especially the thymine residues. Appreciable oxidation can occur without change of sedimentation coefficient.

  10. Ferrocene-based guanidine derivatives: in vitro antimicrobial, DNA binding and docking supported urease inhibition studies.

    Science.gov (United States)

    Gul, Rukhsana; Rauf, Muhammad Khawar; Badshah, Amin; Azam, Syed Sikander; Tahir, Muhammad Nawaz; Khan, Azim

    2014-10-06

    Some novel ferrocenyl guanidines 1-8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with biological macro-molecules like DNA that described to inherit good biological activities. The DNA interaction studies carried out by cyclic voltammetry (CV) and UV-visible spectroscopy are in close agreement with the binding constants (K) (0.79-5.4) × 10(5) (CV) and (0.72-5.1) × 10(5) (UV-vis). The shift in peak potential, current and absorption maxima of the studied ferrocenyl guanidines in the presence of DNA revealed that CV coupled with UV-vis spectroscopy could provide an opportune to characterize metal-based compounds-DNA interaction mechanism, a prerequisite for the design of new anticancer agents and understanding the molecular basis of their action. The compounds 1-8 have been screened for their antibacterial, antifungal and urease inhibition potency. A concurrent in silico study has also been applied on ferrocene moiety impregnated guanidines 1-8 to identify most active compounds having for inhibiting the activity of urease (pdb id 3LA4). Most of the compounds were found as potent inhibitors of urease and the compound 1 was found to be the most active with an IC50 of 16.83 ± 0.03 μM. The docking scores are in close agreement with the in vitro obtained IC50 values of inhibitors 1-8. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Kinetics of electron transfer through ferrocene-terminated alkanethiol monolayers on gold

    Energy Technology Data Exchange (ETDEWEB)

    Smalley, J.F.; Feldberg, S.W.; Newton, M.D.; Liu, Y.P. [Brookhaven National Lab., Upton, NY (United States); Chidsey, C.E.D.; Linford, M.R. [Stanford Univ., CA (United States)

    1995-08-31

    The kinetics of electron transfer between a substrate gold electrode and a self-assembled monolayer formed from CH{sub 3}(CH{sub 2}){sub n-1}SH and ({eta}{sup 5} C{sub 5}H{sub 5})Fe ({eta}{sup 5}-C{sub 5}H{sub 4})CO{sub 2}(CH{sub 2}){sub n}SH were studied as a function of n, the number of methylenes in the alkyl chain tethering the ferrocene moiety to the electrode, using the indirect laser-induced temperature jump method (ILIT). For 5 {<=} n {<=} 9 the standard electron-transfer rate constants vary according to {kappa}{sub {tau}a,n=0} exp[-{beta}{sub n}n] where {kappa}{sub {tau}a,n=0} is the (extrapolated) rate constant for the electron transfer at n = 0. At {Tau} = 25{degree}C, {kappa}{sub {tau}a,n} 0 {approx_equal} 6 x 10{sup 8} s{sup -1} and {beta}{sub n} = 1.21 x 0.05. The ILIT method allows rates to be measured that are too fast to be measured by conventional chronoamperometry at a macroelectrode, which is limited to rate constants of {<=} 10{sup 4} s{sup -1}. Using a Marcus formalism, the reorganization energy, {lambda}, for the electron-transfer process at a given n was determined from the slope of an Arrhenius plot over the temperature range 15-55{degree}C. Values of {lambda} determined from Arrhenius slopes for n = 8 and 9 using ILIT are in reasonable agreement with the value of {lambda} previously deduced from the potential dependence of the rate constant for n = 16. 39 refs., 13 figs., 3 tabs.

  12. Study of superconducting properties of ferrocene-added MgB{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Sudesh; Varma, G.D. [Department of Physics, Indian Institute of Technology Roorkee (India); Das, S.; Bernhard, C. [Department of Physics, Fribourg Centre for Nanomaterials-FriMat, University of Fribourg (Switzerland); Shripathi, T. [UGC-DAE CSR, University Campus, Indore (India)

    2014-07-15

    In the present study, we have shown the effects of ferrocene (FeC{sub 10}H{sub 10}) addition on the superconducting properties of polycrystalline MgB{sub 2} superconductor using transport and magnetic measurements. The addition of FeC{sub 10}H{sub 10} up to 2 wt% in the MgB{sub 2} sample has shown enhanced critical current density, J{sub C} in the entire magnetic field region without affecting much the transition temperature. At 10 K, with respect to a pristine MgB{sub 2} sample, J{sub C} has improved by a factor of 6.55 at 6 T applied field for 1 wt% FeC{sub 10}H{sub 10}. An improvement in the upper critical field, H{sub C{sub 2}} and irreversibility field, H{sub irr} has also been observed up to 2 wt% addition of FeC{sub 10}H{sub 10}. The value of H{sub C{sub 2}} (0) as obtained using the Ginzburg-Landau (GL)-theory fit of the experimental data increases by almost 2 T for 2 wt% FeC{sub 10}H{sub 10}-added MgB{sub 2} as compared to the pristine samples. From X-ray photoemission spectroscopy (XPS), we observed that the Fe is present in sample in the form of ferromagnetic oxides, Fe{sub 3}O{sub 4} and γ-Fe{sub 2}O{sub 3}. These ferromagnetic inclusions provide efficient pinning centers to improve J{sub C}(H) behavior. The flux pinning mechanisms present in the FeC{sub 10}H{sub 10}-added samples are described and discussed in this paper. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. Formation of Mixed-Ligand Complexes of Pd2+ with Nucleoside 5'-Monophosphates and Some Metal-Ion-Binding Nucleoside Surrogates

    Directory of Open Access Journals (Sweden)

    Oleg Golubev

    2014-10-01

    Full Text Available Formation of mixed-ligand Pd2+ complexes between canonical nucleoside 5'-monophosphates and five metal-ion-binding nucleoside analogs has been studied by 1H-NMR spectroscopy to test the ability of these nucleoside surrogates to discriminate between unmodified nucleobases by Pd2+-mediated base pairing. The nucleoside analogs studied included 2,6-bis(3,5-dimethylpyrazol-1-yl-, 2,6-bis(1-methylhydrazinyl- and 6-(3,5-dimethylpyrazol-1-yl-substituted 9-(β-d-ribofuranosylpurines 1–3, and 2,4-bis(3,5-dimethylpyrazol-1-yl- and 2,4-bis(1-methylhydrazinyl-substituted 5-(β-d-ribofuranosyl-pyrimidines 4–5. Among these, the purine derivatives 1-3 bound Pd2+ much more tightly than the pyrimidine derivatives 4, 5 despite apparently similar structures of the potential coordination sites. Compounds 1 and 2 formed markedly stable mixed-ligand Pd2+ complexes with UMP and GMP, UMP binding favored by 1 and GMP by 2. With 3, formation of mixed-ligand complexes was retarded by binding of two molecules of 3 to Pd2+.

  14. Immobilization of Glucose Oxidase on a Carbon Nanotubes/Dendrimer-Ferrocene Modified Electrode for Reagentless Glucose Biosensing.

    Science.gov (United States)

    Zhou, Juan; Li, Huan; Yang, Huasong; Cheng, Hui; Lai, Guosong

    2017-01-01

    Ferrocene-grafted dendrimer was covalently linked to the surface of a carbon nanotubes (CNTs)-chitosan (CS) nanocomposite modified electrode for immobilizing high-content glucose oxidase (GOx), which resulted in the successful development a novel reagentless glucose biosensor. Electrochemical impedance spectroscopy, cyclic voltammetry, and amperometry were used to characterize the preparation process and the enzymatically catalytic response of this biosensor. Due to the excellent electron transfer acceleration of the CNTs and the high-content loading of the GOx biomolecule and ferrocene mediator on the electrode matrix, this biosensor showed excellent analytical performance such as fast response time less than 10 s, wide linear range from 0.02 to 2.91 mM and low detection limit down to 7.5 μM as well as satisfactory stability and reproducibility toward the amperometric glucose determination. In addition, satisfactory result was obtained when it was used for the glucose measurements in human blood samples. Thus this biosensor provides great potentials for practical applications.

  15. Ferrocene-quinoxaline Y-shaped chromophores as fascinating second-order NLO building blocks for long lasting highly active SHG polymeric films.

    Science.gov (United States)

    Senthilkumar, Kabali; Thirumoorthy, Krishnan; Dragonetti, Claudia; Marinotto, Daniele; Righetto, Stefania; Colombo, Alessia; Haukka, Matti; Palanisami, Nallasamy

    2016-07-26

    The first example of a Y-shaped ferrocene quinoxaline derivative with a surprisingly high and stable second harmonic generation (SHG) response in composite polymeric films is reported. The interesting quadratic hyperpolarizability values of different substituted Y-shaped chromophores are also investigated in solution by the EFISH technique.

  16. An ATP-dependent ligase with substrate flexibility involved in assembly of the peptidyl nucleoside antibiotic polyoxin

    Science.gov (United States)

    Polyoxin (POL) is an unusual nucleoside antibiotic, in which peptidyl moiety and nucleoside skeleton are linked by an amide bond. However, their biosynthesis remains poorly understood. Here, we report the deciphering of PolG as an ATP-dependent ligase responsible for the assembly of POL. A polG muta...

  17. Highly regioselective synthesis of undecylenic acid esters of purine nucleosides catalyzed by Candida antarctica lipase B.

    Science.gov (United States)

    Gao, Wen-Li; Li, Ning; Zong, Min-Hua

    2011-11-01

    Regioselective undecylenoylation of purine nucleosides as potential dual prodrugs was achieved by Candida antarctica lipase B using adenosine as a model reactant. The optimum organic solvent, molar ratio of vinyl ester to nucleoside, enzyme dosage, reaction temperature and molecular sieve amount were anhydrous THF, 5:1, 20 U/ml, 45°C and 75 mg/ml, respectively. Under the optimum conditions, the initial reaction rate, yield and 5'-regioselectivity were 1.1 mM/h, 90% and >99%, respectively. The enzymatic acylation of various nucleosides furnished the desired 5'-ester derivatives with the yields of 60-95% and 5'-regioselectivities of >99%. In addition, the lipase displayed excellent operational stability in THF, and retained 96% of its initial activity after reused for five batches.

  18. Characterization of nucleosides and nucleobases in fruits of Ziziphus jujuba by UPLC-DAD-MS.

    Science.gov (United States)

    Guo, Sheng; Duan, Jin-Ao; Tang, Yu-Ping; Zhu, Zhen-Hua; Qian, Ye-Fei; Yang, Nian-Yun; Shang, Er-Xin; Qian, Da-Wei

    2010-10-13

    The fruit of Ziziphus jujuba , named dazao in Chinese, has been utilized as food as well as crude drugs in China for thousands of years. To explore the profiles of the nucleosides and nucleobases in this fruit, an ultraperformance liquid chromatograph coupled with a photodiode array detector and electrospray ionization-mass spectrometer method (UPLC-DAD-MS) has been established and validated in this paper. The validated method was successfully applied for the simultaneous characterization and quantitation of 9 nucleosides and nucleobases in 49 dazao samples, which comprised 43 cultivars from 26 cultivation regions. Furthermore, principal component analysis (PCA) was performed to classify the samples on the basis of the contents of the nine analyzed compounds. The results showed that almost all of these dazao samples were rich in nucleosides and nucleobases, although their contents were obviously various, and the proposed method could serve as a prerequisite for quality control of jujube products.

  19. Synthesis and antiviral activity of 3'-deoxy-3'-C-hydroxymethyl nucleosides.

    Science.gov (United States)

    Bamford, M J; Coe, P L; Walker, R T

    1990-09-01

    A series of 3'-branched-chain sugar nucleosides, in particular 3'-deoxy-3'-C-hydroxmethyl nucleosides, have been synthesized and evaluated as antiviral agents. Reaction of 1-(2,3-epoxy-5-O-trityl-beta-D-lyxo-pentofuranosyl) derivatives 12 and 13, of uracil and thymine, respectively, with 5,6-dihydro-2-lithio-5-methyl-1,3,5-dithiazine 14 afforded the corresponding 3'-functionalized nucleosides 15 and 16, respectively. Replacement of the trityl group with tertbutyldiphenylsilyl allowed high yielding hydrolysis of the 3'-function to give the 3'-deoxy-3'-C-formyl-beta-D-arabino-pentofuranosyl nucleosides 21 and 22. Desilylation afforded the 1-(3-deoxy-3-C-formyl-beta- D-lyxo-pentofuranosyl) 3',5'-O-hemiacetal nucleosides 33 and 34, respectively. Reduction of the formyl group of 21 and 22, followed by desilylation, yielded the 3'-deoxy-3'-C-(hydroxymethyl)-beta-D-arabino- pentofuranosyl) analogues 7 and 8, respectively. The uracil base moiety of 7 was converted to 5-iodouracil and then to (E)-5-(2-bromovinyl)uracil to furnish an analogue 10 of BVaraU. The 1-(3-deoxy-3-C-(hydroxymethyl)-beta-D-lyxo-pentofuranosyl) and 1-(2,3-dideoxy-3-C-(hydroxymethyl)-beta-D-erythro-pentofuranosyl) derivatives of uracil (31 and 6, respectively) and 5-iodouracil (32 and 9, respectively) were also obtained. All novel, fully deprotected nucleoside analogues were evaluated for antiviral activity against human immunodeficiency virus type-1, herpes simplex virus types-1 and -2, varicella zoster virus, human cytomegalovirus and influenza A. Of the compounds tested only (E)-5-(2-bromovinyl)-1-[3-deoxy- 3-C-(hydroxymethyl)-beta-D-arabino-pentofuranosyl]uracil (10) inhibited VZV (alone), but did so at concentrations well below the cytotoxicity threshold.

  20. Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

    Directory of Open Access Journals (Sweden)

    Qiang Yu

    2008-12-01

    Full Text Available Enantioselective syntheses from dimethyl tartrate of 1,3,5-triazine homo-N-nucleoside analogs, containing a 1,4-dioxane moiety replacing the sugar unit in natural nucleosides, were accomplished. The triazine heterocycle in the nucleoside analogs was further substituted with combinations of NH2, OH and Cl in the 2,4-triazine positions.

  1. Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

    Directory of Open Access Journals (Sweden)

    Vicky Gheerardijn

    2014-11-01

    Full Text Available Functionalized oligonucleotides have recently gained increased attention for incorporation in modified nucleic acid structures both for the design of aptamers with enhanced binding properties as well as the construction of catalytic DNA and RNA. As a shortcut alternative to the incorporation of multiple modified residues, each bearing one extra functional group, we present here a straightforward method for direct linking of functionalized amino acids to the nucleoside base, thus equipping the nucleoside with two extra functionalities at once. As a proof of principle, we have introduced three amino acids with functional groups frequently used as key-intermediates in DNA- and RNAzymes via an efficient and straightforward domino carboxamidation reaction.

  2. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

    DEFF Research Database (Denmark)

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral

    2012-01-01

    The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.......The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....

  3. Mutagenicity of irradiated solutions of nuclei acid bases and nucleosides in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Wilmer, J.; Schubert, J.

    1981-01-01

    Solutions of nucleic acid bases, nucleosides and a nucleotide, saturated with either N 2 , N 2 O or O 2 , were irradiated and tested for mutagenicity towards Salmonella typhimurium, with and without pre-incubation. Irradiated solutions of the nuclei acid bases were all non-mutagenic. Irradiated solutions of the nucleosides showed mutagenicity in S. typhimurium TA100 (pre-incubation assay). Generally, the mutagenicity followed the order: N 2 O > N 2 > O 2 . The results show that the formation of mutagenic radiolytic products is initiated by attack of mainly solutions of the nucleotide thymidine-5'-monophosphate, no mutagenicity could be detected. (orig.)

  4. Anopheles gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure, and Inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Taylor,E.; Rinaldo-Matthis, A.; Li, L.; Ghanem, M.; Hazleton, K.; Cassera, M.; Almo, S.; Schramm, V.

    2007-01-01

    The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for AgPNP at 226 s-1 for guanosine in pre-steady-state studies. 5'-Deaza-1'-aza-2'-deoxy-1'-(9-methylene)-Immucillin-H (DADMe-ImmH) is a transition-state mimic for a 2'-deoxyinosine ribocation with a fully dissociated N-ribosidic bond and is a slow-onset, tight-binding inhibitor with a dissociation constant of 3.5 pM. This is the tightest-binding inhibitor known for any PNP, with a remarkable Km/Ki* of 5.4 x 107, and is consistent with enzymatic transition state predictions of enhanced transition-state analogue binding in enzymes with enhanced catalytic efficiency. Deoxyguanosine is a weaker substrate than deoxyinosine, and DADMe-Immucillin-G is less tightly bound than DADMe-ImmH, with a dissociation constant of 23 pM for AgPNP as compared to 7 pM for HsPNP. The crystal structure of AgPNP was determined in complex with DADMe-ImmH and phosphate to a resolution of 2.2 Angstroms to reveal the differences in substrate and inhibitor specificity. The distance from the N1' cation to the phosphate O4 anion is shorter in the AgPNP{center_dot}DADMe-ImmH{center_dot}PO4 complex than in HsPNP{center_dot}DADMe-ImmH{center_dot}SO4, offering one explanation for the stronger inhibitory effect of DADMe-ImmH for AgPNP.

  5. Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

    Science.gov (United States)

    Pauly, Matthew D; Lauring, Adam S

    2015-04-01

    Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

  6. Food labels

    DEFF Research Database (Denmark)

    Selsøe Sørensen, Henrik; Clement, Jesper; Gabrielsen, Gorm

    2012-01-01

    evidence for dividing consumers into two profiles: one relying on general food knowledge and another using knowledge related to signpost labels. In a combined eyetracking and questionnaire survey we analyse the influence of background knowledge and identify different patterns of visual attention......The food industry develops tasty and healthy food but fails to deliver the message to all consumers. The consumers’ background knowledge is essential for how they find and decode relevant elements in the cocktail of signs which fight for attention on food labels. In this exploratory study, we find...... for the two consumer profiles. This underlines the complexity in choosing and designing the ‘right’ elements for a food package that consumers actually look at and are able to make rational use of. In spite of any regulation of food information provided by authorities, consumers will still be confronted...

  7. Peeling off effects in vertically aligned Fe3C filled carbon nanotubes films grown by pyrolysis of ferrocene

    Science.gov (United States)

    Boi, Filippo S.; Medranda, Daniel; Ivaturi, Sameera; Wang, Jiayu; Guo, Jian; Lan, Mu; Wen, Jiqiu; Wang, Shanling; He, Yi; Mountjoy, Gavin; Willis, Maureen A. C.; Xiang, Gang

    2017-06-01

    We report the observation of an unusual self-peeling effect which allows the synthesis of free standing vertically aligned carbon nanotube films filled with large quantities of Fe3C and small quantities of γ-Fe crystals. We demonstrate that this effect depends on the interplay of three main factors: (1) the physical interactions between the chosen substrate surface and grown carbon nanotubes (CNTs), which is fixed by the composition of the used substrate (111 SiO2/Si or quartz), (2) the CNT-CNT Van der Waals interactions, and (3) the differential thermal contraction between the grown CNT film and the used substrate, which is fixed by the cooling rate differences between the grown film and the used quartz or Si/SiO2 substrates. The width and stability of these films are then further increased to cm-scale by addition of small quantities of toluene to the ferrocene precursor.

  8. Analyses of residual iron in carbon nanotubes produced by camphor/ferrocene pyrolysis and purified by high temperature annealing

    Energy Technology Data Exchange (ETDEWEB)

    Antunes, E.F., E-mail: ericafa@las.inpe.br [Instituto Tecnologico de Aeronautica (ITA), Praca Marechal Eduardo Gomes, 50, CEP 12.228-900, Sao Jose dos Campos, SP (Brazil); Instituto Nacional de Pesquisas Espaciais (INPE), Av. dos Astronautas, 1758, CEP 12.227-010, Sao Jose dos Campos, SP (Brazil); Resende, V.G. de; Mengui, U.A. [Instituto Nacional de Pesquisas Espaciais (INPE), Av. dos Astronautas, 1758, CEP 12.227-010, Sao Jose dos Campos, SP (Brazil); Cunha, J.B.M. [Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Goncalves, 9500, CEP 91.501-970, Porto Alegre, RS (Brazil); Corat, E.J.; Massi, M. [Instituto Nacional de Pesquisas Espaciais (INPE), Av. dos Astronautas, 1758, CEP 12.227-010, Sao Jose dos Campos, SP (Brazil)

    2011-07-01

    A detailed analysis of iron-containing phases in multiwall carbon nanotube (MWCNT) powder was carried out. The MWCNTs were produced by camphor/ferrocene and purified by high temperature annealing in an oxygen-free atmosphere (N{sub 2} or VC). Thermogravimetric analysis, Moessbauer spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy enabled the evaluation of the residual iron in MWCNTs after purification. The VC treatments provided MWCNTs with a purity degree higher than 99%. Moreover, Raman spectroscopy revealed a significant improvement in graphitic ordering after thermal annealing. A brief description of the mechanism of iron removal was included. We highlight the mobility of iron atoms through graphitic sheets and the large contact angle of iron clusters formed on MWCNT surfaces at high temperatures.

  9. A Ferrocene-Based Catecholamide Ligand: the Consequences of Ligand Swivel for Directed Supramolecular Self-Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Mugridge, Jeffrey; Fiedler, Dorothea; Raymond, Kenneth

    2010-02-04

    A ferrocene-based biscatecholamide ligand was prepared and investigated for the formation of metal-ligand supramolecular assemblies with different metals. Reaction with Ge(IV) resulted in the formation of a variety of Ge{sub n}L{sub m} coordination complexes, including [Ge{sub 2}L{sub 3}]{sup 4-} and [Ge{sub 2}L{sub 2}({mu}-OMe){sub 2}]{sup 2-}. The ligand's ability to swivel about the ferrocenyl linker and adopt different conformations accounts for formation of many different Ge{sub n}L{sub m} species. This study demonstrates why conformational ligand rigidity is essential in the rational design and directed self-assembly of supramolecular complexes.

  10. N-Branched acyclic nucleoside phosphonates as monomers for the synthesis of modified oligonucleotides

    Czech Academy of Sciences Publication Activity Database

    Hocková, Dana; Rosenbergová, Šárka; Ménová, Petra; Páv, Ondřej; Pohl, Radek; Novák, Pavel; Rosenberg, Ivan

    2015-01-01

    Roč. 13, č. 15 (2015), s. 4449-4458 ISSN 1477-0520 R&D Projects: GA ČR GAP207/11/0108; GA ČR GA13-26526S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * oligonucleotides * solid phase synthesis Subject RIV: CC - Organic Chemistry Impact factor: 3.559, year: 2015

  11. High yield expression and purification of equilibrative nucleoside transporter 7 (ENT7) from Arabidopsis thaliana.

    Science.gov (United States)

    Girke, Christopher; Arutyunova, Elena; Syed, Maria; Traub, Michaela; Möhlmann, Torsten; Lemieux, M Joanne

    2015-09-01

    Equilibrative nucleoside transporters (ENTs) facilitate the import of nucleosides and their analogs into cells in a bidirectional, non-concentrative manner. However, in contrast to their name, most characterized plant ENTs act in a concentrative manner. A direct characterization of any ENT protein has been hindered due to difficulties in overexpression and obtaining pure recombinant protein. The equilibrative nucleoside transporter 7 from Arabidopsis thaliana (AtENT7) was expressed in Xenopus laevis oocytes to assess mechanism of substrate uptake. Recombinant protein fused to enhanced green fluorescent protein (eGFP) was expressed in Pichia pastoris to characterize its oligomeric state by gel filtration and substrate binding by microscale thermophoresis (MST). AtENT7 expressed in X. laevis oocytes works as a classic equilibrative transporter. The expression of AtENT7-eGFP in the P. pastoris system yielded milligram amounts of pure protein that exists as stable homodimers. The concentration dependent binding of purine and pyrimidine nucleosides to the purified recombinant protein, assessed by MST, confirmed that AtENT7-eGFP is properly folded. For the first time the binding of nucleobases was observed for AtENT7. The availability of pure recombinant AtENT7 will permit detailed kinetic and structural studies of this unique member of the ENT family and, given the functional similarity to mammalian ENTs, will serve as a good model for understanding the structural basis of translocation mechanism for the family. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3.

    Czech Academy of Sciences Publication Activity Database

    Potměšil, Petr; Holý, Antonín; Kmoníčková, Eva; Křížková, Jana; Zídek, Zdeněk

    2007-01-01

    Roč. 14, č. 1 (2007), s. 59-66 ISSN 1021-7770 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40550506 Keywords : Acyclic nucleoside phosponate * HIV * Monocyte chemotactic protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.024, year: 2007

  13. Nucleoside analogue 2’-C-methylcytidine inhibits hepatitis E virus replication but antagonizes ribavirin

    NARCIS (Netherlands)

    Qu, C. (Changbo); L. Xu (Lei); Y. Yin (Yuebang); M.P. Peppelenbosch (Maikel); Q. Pan (Qiuwei); W. Wang (Wenshi)

    2017-01-01

    textabstractHepatitis E virus (HEV) infection has emerged as a global health issue, but no approved medication is available. The nucleoside analogue 2’-C-methylcytidine (2CMC), a viral polymerase inhibitor, has been shown to inhibit infection with a variety of viruses, including hepatitis C virus

  14. Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in vitro

    DEFF Research Database (Denmark)

    Engel, M; Issinger, O G; Lascu, I

    1994-01-01

    We have investigated phosphorylation of human nucleoside diphosphate kinase (NDPK) and of homologous NDPK from different species by human casein kinase 2 (CK-2). The human NDPK isotypes A and B were phosphorylated by CK-2 in vitro both when the purified proteins and total lysate of HL-60 leukemia...

  15. Inhibition of the Escherichia coli 6-oxopurine phosphoribosyltransferases by nucleoside phosphonates: potential for new antibacterial agents

    Czech Academy of Sciences Publication Activity Database

    Keough, D. T.; Hocková, Dana; Rejman, Dominik; Špaček, Petr; Vrbková, Silvie; Krečmerová, Marcela; Eng, W. S.; Jans, H.; West, N. P.; Naesens, L. M. J.; de Jersey, J.; Guddat, L. W.

    2013-01-01

    Roč. 56, č. 17 (2013), s. 6967-6984 ISSN 0022-2623 R&D Projects: GA ČR GAP207/11/0108 Institutional support: RVO:61388963 Keywords : nucleoside phosphonates * antibacterial agents * hypoxanthine-guanine phosphoribosyltransferase * state analog inhibitor * antimalarial chemotherapy Subject RIV: CC - Organic Chemistry Impact factor: 5.480, year: 2013

  16. Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic nucleoside phosphonates: A new class of antimalarial therapeutics

    Czech Academy of Sciences Publication Activity Database

    Keough, D. T.; Hocková, Dana; Holý, Antonín; Naesens, L.; Skinner-Adams, T. S.; de Jersey, J.; Guddat, L. W.

    2009-01-01

    Roč. 52, č. 14 (2009), s. 4391-4399 ISSN 0022-2623 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * phosphoribosyltransferase * enzyme inhibitors * Plasmodium falciparum Subject RIV: CC - Organic Chemistry Impact factor: 4.802, year: 2009

  17. Antiretrovirus activity of a novel class of acyclic pyrimidine nucleoside phosphonates

    Czech Academy of Sciences Publication Activity Database

    Balzarini, J.; Pannecouque, C.; De Clercq, E.; Aquaro, S.; Perno, C. F.; Egberink, H.; Holý, Antonín

    2002-01-01

    Roč. 46, č. 7 (2002), s. 2185-2193 ISSN 0066-4804 R&D Projects: GA ČR GV203/96/K001 Institutional research plan: CEZ:AV0Z4055905 Keywords : nucleoside phosphonates Subject RIV: CC - Organic Chemistry Impact factor: 4.215, year: 2002

  18. Norbornane-based nucleoside and nucleotide analogues locked in North conformation

    Czech Academy of Sciences Publication Activity Database

    Dejmek, Milan; Šála, Michal; Hřebabecký, Hubert; Dračínský, Martin; Procházková, Eliška; Chalupská, Dominika; Klíma, Martin; Plačková, Pavla; Hájek, Miroslav; Andrei, G.; Naesens, L.; Leyssen, P.; Neyts, J.; Balzarini, J.; Bouřa, Evžen; Nencka, Radim

    2015-01-01

    Roč. 23, č. 1 (2015), s. 184-191 ISSN 0968-0896 R&D Projects: GA ČR GPP207/12/P625; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : carbocyclic nucleosides * purines * norbornane * antiviral * PI4KIIalpha Subject RIV: CC - Organic Chemistry Impact factor: 2.923, year: 2015

  19. Design and Synthesis of Fluorescent Acyclic Nucleoside Phosphonates as Potent Inhibitors of Bacterial Adenylate Cyclases

    Czech Academy of Sciences Publication Activity Database

    Břehová, Petra; Šmídková, Markéta; Skácel, Jan; Dračínský, Martin; Mertlíková-Kaiserová, Helena; Velasquez, M. P. S.; Watts, V. J.; Janeba, Zlatko

    2016-01-01

    Roč. 11, č. 22 (2016), s. 2534-2546 ISSN 1860-7179 R&D Projects: GA MV VG20102015046; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : adenylate cyclase toxin * acyclic nucleoside phosphonates * anthranilic acid Subject RIV: CC - Organic Chemistry Impact factor: 3.225, year: 2016

  20. Synthesis of 2'-deoxyuridine and 2'-deoxycytidine nucleosides bearing bipyridine and terpyridine ligands in position 5

    Czech Academy of Sciences Publication Activity Database

    Kalachová, Lubica; Pohl, Radek; Hocek, Michal

    -, č. 1 (2009), s. 105-112 ISSN 0039-7881 R&D Projects: GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * pyrimidines * cross-coupling * bipyridine s Subject RIV: CC - Organic Chemistry Impact factor: 2.572, year: 2009

  1. Secretion of antiretroviral chemokines by human cells cultured with acyclic nucleoside phosphonates

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Kmoníčková, Eva; Holý, Antonín

    2007-01-01

    Roč. 574, - (2007), s. 77-84 ISSN 0014-2999 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40550506 Keywords : Acyclic nucleoside phosphonate * Chemokine * Cytokine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.376, year: 2007

  2. Interactions of trimeric purine nucleoside phosphorylases with ground state analogues - calorimetric and fluorimetric studies

    Czech Academy of Sciences Publication Activity Database

    Wielgus-Kutrowska, B.; Frank, J.; Holý, Antonín; Koellner, G.; Bzowska, A.

    2003-01-01

    Roč. 22, 5/8 (2003), s. 1695-1698 ISSN 1525-7770 Grant - others:PCSR(PL) 6 P04A04416; PCSR(PL) 3 P04A03524 Institutional research plan: CEZ:AV0Z4055905 Keywords : purine nucleoside phosphorylase * fluorescence Subject RIV: CC - Organic Chemistry Impact factor: 0.813, year: 2003

  3. ACTIVATION OF G-PROTEINS BY RECEPTOR-STIMULATED NUCLEOSIDE DIPHOSPHATE KINASE IN DICTYOSTELIUM

    NARCIS (Netherlands)

    Bominaar, Anthony A.; Molijn, Anco C.; Pestel, Martine; Veron, Michel; Haastert, Peter J.M. van

    Recently, interest in the enzyme nucleoside diphosphate kinase (EC 2.7.4.6) has increased as a result of its possible involvement in cell proliferation and development. Since NDP kinase is one of the major sources of GTP in cells, it has been suggested that the effects of an altered NDP kinase

  4. Aspartic acid based nucleoside phosphoramidate prodrugs as potent inhibitors of hepatitis C virus replication.

    Science.gov (United States)

    Maiti, Munmun; Maiti, Mohitosh; Rozenski, Jef; De Jonghe, Steven; Herdewijn, Piet

    2015-05-14

    In view of a persistent threat to mankind, the development of nucleotide-based prodrugs against hepatitis C virus (HCV) is considered as a constant effort in many medicinal chemistry groups. In an attempt to identify novel nucleoside phosphoramidate analogues for improving the anti-HCV activity, we have explored, for the first time, aspartic acid (Asp) and iminodiacetic acid (IDA) esters as amidate counterparts by considering three 2'-C-methyl containing nucleosides, 2'-C-Me-cytidine, 2'-C-Me-uridine and 2'-C-Me-2'-fluoro-uridine. Synthesis of these analogues required protection for the vicinal diol functionality of the sugar moiety and the amino group of the cytidine nucleoside to regioselectively perform phosphorylation reaction at the 5'-hydroxyl group. Anti-HCV data demonstrate that the Asp-based phosphoramidates are ∼550 fold more potent than the parent nucleosides. The inhibitory activity of the Asp-ProTides was higher than the Ala-ProTides, suggesting that Asp would be a potential amino acid candidate to be considered for developing novel antiviral prodrugs.

  5. beta-1,2,3-Triazolyl-Nucleosides as Nicotinamide Riboside Mimics

    Czech Academy of Sciences Publication Activity Database

    Amigues, E.J.; Armstrong, E.; Dvořáková, Marcela; Migaud, M.E.; Huang, M.

    2009-01-01

    Roč. 28, č. 3 (2009), s. 238-259 ISSN 1525-7770 Institutional research plan: CEZ:AV0Z50380511 Keywords : Nucleoside * nucleotide * sirtuin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.768, year: 2009

  6. Synthesis and NMR spectral studies if some nucleosides and their analoges

    International Nuclear Information System (INIS)

    Ansari, F.L.; Awan, H.S.; Kazmi, N.A.

    1995-01-01

    Massive efforts have been extended towards the analysis of nucleosides due mainly to their applications in the field of medicine. Present work describes two methods for the synthesis of nucleosides and their analogues. The first method involves the use of phase transfer catalysis for the glycosidation of benzimidazoles. The reaction of 2,3,5-tri-o-benzoyl-beta -d-arabinofuranosyl chloride with benzimidazole and 2 (alpha-hydroxyethyl) benzimidazole in the presence of tetrabutylammoniumhydroensulfide led to the synthesis of nucleosides respectively. Likewise the coupling of 1,2:4, 6-di-O-isopropylidene-3-chloro-alpha-D-fructofurano side with benzimidazole led to the desired product. The second method involves a triflate mediated coupling of benzyl-2,3-anhydro-4-O-triflyl-beta-L-ribopyranoside with benzimidazole which led to the facile displacement of the triflyl group with benzimidazole resulting in the synthesis of nucleoside. However, an attempt towards the coupling of 1,2:5,6-di-O-isopropylidene-3-O-triflyl-alpha-D-glucofuranoside with benzimidazole does not led to the desired coupling, instead an unusual conversion of the triflate ester to mesitylate ester of the sugar appears to have been taken place. (author)

  7. Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase

    DEFF Research Database (Denmark)

    Mikkelsen, Niels Egil; Munch-Petersen, Birgitte; Eklund, Hans

    2008-01-01

    -drug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. Here we present crystal structures of dNK complexed with four different nucleoside analogs floxuridine (5FdU), brivudine (BVDU), zidovudine (AZT) and zalcitabine (ddC...

  8. Detergent inhibited, heat labile nucleoside triphosphatase in cores of avian myeloblastosis virus

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank

    1978-01-01

    Endogenous DNA synthesis was studied in isolated core particles of avian myeloblastosis virus. It was found that cores contained an enzymatic activity which rapidly converted the added nucleoside triphosphates to diphosphates (but not further) at 0 degrees C, thus inhibiting DNA synthesis...

  9. Computational and Pharmacological Evaluation of Ferrocene-Based Acyl Ureas and Homoleptic Cadmium Carboxylate Derivatives for Anti-diabetic Potential

    Directory of Open Access Journals (Sweden)

    Shahar Bano

    2018-01-01

    Full Text Available We investigated possible anti-diabetic effect of ferrocene-based acyl ureas: 4-ferrocenyl aniline (PFA, 1-(4-chlorobenzoyl-3-(4-ferrocenylphenyl urea (DPC1, 1-(3-chlorobenzoyl-3-(4-ferrocenylphenyl urea (DMC1, 1-(2-chlorobenzoyl-3-(4-ferrocenylphenyl urea (DOC1 and homoleptic cadmium carboxylates: bis (diphenylacetato cadmium (II (DPAA, bis (4-chlorophenylacetato cadmium (II (CPAA, using in silico and in vivo techniques. PFA, DPC1, DMC1, DOC1, DPAA and CPAA exhibited high binding affinities (ACE ≥ −350 Kcal/mol against targets: aldose reductase, peroxisome proliferator-activated receptor γ, 11β-hydroxysteroid dehydrogenase-1, C-alpha glucosidase and glucokinase, while showed moderate affinities (ACE ≥ −250 Kcal/mol against N-alpha glucosidase, dipeptidyl peptidase-IV, phosphorylated-Akt, glycogen synthase kinase-3β, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, whereas revealed lower affinities (ACE < −250 Kcal/mol vs. alpha amylase, protein tyrosine phosphatases 1B, glycogen phosphorylase and phosphatidylinositol 3 kinase. In alloxan (300 mg/Kg-induced diabetic mice, DPAA and DPC1 (1–10 mg/Kg at day 1, 5, 10, 15, and 20th decreased blood glucose levels, compared to diabetic control group and improved the treated animals body weight. DPAA (10 mg/Kg and DPC1 (5 mg/Kg in time-dependent manner (30–120 min. enhanced tolerance of oral glucose overload in mice. DPAA and DPCI dose-dependently at 1, 5, and 10 mg/Kg decreased glycosylated hemoglobin levels in diabetic animals, as caused by metformin. These results indicate that aforementioned derivatives of ferrocene and cadmium possess anti-diabetic potential.

  10. A ferrocene functionalized polymer: Poly [N-(ferrocenylmethyl)-o-phenylenediamine]. Electrochemical production and spectroelectroelectrochemical investigation in acetonitrile medium

    International Nuclear Information System (INIS)

    Gülce, Handan; Yetkin, Ahmet; Akgül, Eda; Gülce, Ahmet

    2013-01-01

    An electroactive and conductive polymer having pendant ferrocene units was prepared from the electrochemical polymerization of the synthesized monomer, N-(ferrocenylmethyl)-o-phenylenediamine in 0.1 M tetrabuthylammonium perchlorate/acetonitrile medium. The poly-N-(ferrocenylmethyl)-o-phenylenediamine (poly-FMOPD) was generated potentiodynamically or potentiostatically at both of indium tin oxide coated glass substrate and Pt electrodes. The poly-FMOPD film was characterized by cyclic voltammetry, chronoamperometry, electrochemical impedance spectroscopy, dry conductivity measurements, ultraviolet–visible absorption spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy. The electrical conductivity of polymer films was determined as 1.0 × 10 −1 and 4 × 10 −2 S cm −1 depending on the potential scanning range during electropolymerization. The electroactivity of the polymer film retained even after hundreds cycles between their reduced and oxidized states. The spectroelectrochemical analysis demonstrated that the polymer film reveals a reversible cycling with distinctive color changes between neutral and reduced/oxidized forms. For the polymer film, the maximum optical contrasts (ΔT%) were measured as 18% at and 37% at 480 nm by step the potential between (0.00 V)-(1.20 V) and (− 0.50 V)-(− 1.70 V), respectively. The optical energy band gaps as the onset energy for the π–π* transitions are calculated as 1.89 eV, 1.85 eV and 1.88 eV for the neutral, reduced and oxidized states of poly-FMOPD. - Highlights: • The ferrocene functionalized monomer and its polymer were synthesized electrochemically. • Spectroelectrochemical investigations were performed. • The polymer film showed reversible color changes between different redox forms. • It was found that the polymer film is conductive

  11. An Electrochemical DNA Biosensor for the Detection of Salmonella Using Polymeric Films and Electrochemical Labels

    Science.gov (United States)

    Diaz Serrano, Madeline

    Waterborne and foodborne diseases are one of the principal public health problems worldwide. Microorganisms are the major agents of foodborne illness: pathogens such as Salmonella, Campylobacter jejuni and Escherichia coli, and parasites such as cryptosporidium. The most popular methods to detect Salmonella are based on culture and colony counting methods, ELISA, Gel electrophoresis and the polymerase chain reaction. Conventional detection methods are laborious and time-consuming, allowing for portions of the food to be distributed, marketed, sold and eaten before the analysis is done and the problem even detected. By these reasons, the rapid, easy and portable detection of foodborne organisms will facilitate the disease treatment. Our particular interest is to develop a nucleic acid biosensor (NAB) for the detection of pathogenic microorganisms in food and water samples. In this research, we report on the development of a NAB prototype using a polymer modified electrode surface together with sequences of different lengths for the OmpC gene from Salmonella as probes and Ferrocene-labeled target (Fc-ssDNA), Ferrocene-labeled tri(ethylene glycol) (Fc-PEG) and Ruthenium-Ferrocene (Ru-Fe) bimetallic complex as an electrochemical labels. We have optimized several PS films and anchored nucleic acid sequences with different lengths at gold and carbon surfaces. Non contact mode AFM and XPS were used to monitor each step of the NAB preparation, from polymer modification to oligos hybridization (conventional design). The hybridization reaction was followed electrochemically using a Fc-ssDNA and Fc-PEG in solution taking advantage of the morphological changes generated upon hybridization. We observed a small current at the potential for the Fe oxidation without signal amplification at +296 mV vs. Ag/AgCl for the Fc-ssDNA strategy and a small current at +524 mV for the Fc-PEG strategy. The immobilization, hybridization and signal amplification of Biotin- OmpC Salmonella genes

  12. Pyrimidine nucleoside analogues, potential chemotherapeutic agents, and substrates/inhibitors in various enzyme systems

    International Nuclear Information System (INIS)

    Kulikowski, T.; Bretner, M.; Felczak, K.; Drabikowska, A.; Shugar, D.

    1998-01-01

    Full text. Pyrimidine nucleoside analogues are an important class of compounds with antimetabolic (antitumor, antiparasitic and antiviral) properties. The synthesis of thiated nucleoside and nucleotide analogues, determination of structures, conformation and dissociation constans, their potential chemotherapeutic activities, and their substrate/inhibitor properties in various enzyme systems, with emphasis on enzymes related to chemotherapeutic activities, were investigated. In the series of thionated inhibitors of thymidylate synthase (TS), potential antitumor agents, regioselective syntheses were elaborated for 2- and 4-thio, and 2,4-dithio derivatives of 2'-deoxyuridine (dUrd), 5-fluoro-2'-deoxyuridine (FdUrd), and several other 5-fluoro-, 5-bromo- and 5-trifluoromethyl congeners, and the 2-thio derivatives of FdUrd and its α-anomer, which proved to be selective agents with high cytotoxicities correlated with the inhibitory activities vs TS of their corresponding 5'-monophosphates. Regioslective syntheses were also elaborated for 2'-deoxycytidin e and 5-fluoro-2'-deoxycitidine derivatives. Solution conformation of these nucleosides were deduced from high-resolution (500 MHz) 1 H NMR spectra. Substrate/inhibitor properties of 2-thio-2'-deoxycitidine (S 2 dCyd) and 5-fluoro-2-thio-2'-deoxycitidine ( S 2 FdCyd) with respect to human leukemic spleen deoxycytidine kinase have been examined. Both are substrates, and also good inhibitors, of phosphorylation of 2'-deoxycitidine and 2'-deoxyadenosine. Particular attention was directed to the specificity of t he NTP phosphate donor for several nucleoside kinases, and procedures have been developed for distinguishing between ATP and other NTP donors, a problem of importance in chemotherapy with nucleoside analogues. Biological properties of the newly synthetize d thiated pyrimidine 2',3'-dideoxy-3'-fluoronucleosides, S 2 ,3'-FddUrd and S 2 ,3'-FddThd, were also investigated. Thiated 3'-fluoronucleosides were moderate

  13. Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels

    Science.gov (United States)

    Lawley, P. D.; Shah, S. A.

    1972-01-01

    1. The following methods for hydrolysis of methyl-14C-labelled RNA, and for chromatographic isolation and determination of the products, were investigated: enzymic digestion to nucleosides at pH6 or 8; alkaline hydrolysis and conversion into nucleosides; hydrolysis by acid to pyrimidine nucleotides and purine bases, or completely to bases; chromatography on Dowex 50 (NH4+ form) at pH6 or 8.9, or on Dowex 50 (H+ form), or on Sephadex G-10. 2. The suitability of the various methods for determination of methylation products was assessed. The principal product, 7-methylguanosine, was unstable under the conditions used for determinations of nucleosides. 3- and 7-Methyladenine and 3- and 7-methylguanine are best determined as bases; 1-methyladenine and 3-methylcytosine can be isolated as either nucleosides or bases; O6-methylguanine is unstable under the acid hydrolysis conditions used and can be determined as the nucleoside; 3-methyluracil was detected, but may be derived from methylation of the ionized form of uracil. 3. Differences between the patterns of methylation of RNA and homopolyribonucleotides by the N-methyl-N-nitroso compounds and dimethyl sulphate were found: the nitroso compounds were able to methylate O-6 of guanine, were relatively more reactive at N-7 of adenine and probably at N-3 of guanine, but less reactive at N-1 of adenine, N-3 of cytosine and probably at N-3 of uridine. They probably reacted more with the ribose–phosphate chain, but no products from this were identified. 4. The possible influences of these differences on biological action of the methylating agents is discussed. Nitroso compounds may differ principally in their ability to induce miscoding in the Watson–Crick sense by reaction at O-6 of guanine. Both types of agent may induce miscoding to a lesser extent through methylation at N-3 of guanine; both can methylate N atoms, presumably preventing Watson–Crick hydrogen-bonding. N-Methyl-N-nitrosourea can degrade RNA, possibly

  14. Label triangulation

    International Nuclear Information System (INIS)

    May, R.P.

    1983-01-01

    Label Triangulation (LT) with neutrons allows the investigation of the quaternary structure of biological multicomponent complexes under native conditions. Provided that the complex can be fully separated into and reconstituted from its single - protonated and deuterated - components, small angle neutron scattering (SANS) can give selective information on shapes and pair distances of these components. Following basic geometrical rules, the spatial arrangement of the components can be reconstructed from these data. LT has so far been successfully applied to the small and large ribosomal subunits and the transcriptase of E. coli. (author)

  15. Structural and thermodynamic analysis of modified nucleosides in self-assembled DNA cross-tiles.

    Science.gov (United States)

    Hakker, Lauren; Marchi, Alexandria N; Harris, Kimberly A; LaBean, Thomas H; Agris, Paul F

    2014-01-01

    DNA Holliday junctions are important natural strand-exchange structures that form during homologous recombination. Immobile four-arm junctions, analogs to Holliday junctions, have been designed to self-assemble into cross-tile structures by maximizing Watson-Crick base pairing and fixed crossover points. The cross-tiles, self-assembled from base pair recognition between designed single-stranded DNAs, form higher order lattice structures through cohesion of self-associating sticky ends. These cross-tiles have 16 unpaired nucleosides in the central loop at the junction of the four duplex stems. The importance of the centralized unpaired nucleosides to the structure's thermodynamic stability and self-assembly is unknown. Cross-tile DNA nanostructures were designed and constructed from nine single-stranded DNAs with four shell strands, four arms, and a central loop containing 16 unpaired bases. The 16 unpaired bases were either 2'-deoxyribothymidines, 2'-O-methylribouridines, or abasic 1',2'-dideoxyribonucleosides. Thermodynamic profiles and structural base-stacking contributions were assessed using UV absorption spectroscopy during thermal denaturation and circular dichroism spectroscopy, respectively, and the resulting structures were observed by atomic force microscopy. There were surprisingly significant changes in the thermodynamic and structural properties of lattice formation as a result of altering only the 16 unpaired, centralized nucleosides. The 16 unpaired 2'-O-methyluridines were stabilizing and produced uniform tubular structures. In contrast, the abasic nucleosides were destabilizing producing a mixture of structures. These results strongly indicate the importance of a small number of centrally located unpaired nucleosides within the structures. Since minor modifications lead to palpable changes in lattice formation, DNA cross-tiles present an easily manipulated structure convenient for applications in biomedical and biosensing devices.

  16. Assessment of nucleosides as putative tumor biomarkers in prostate cancer screening by CE-UV.

    Science.gov (United States)

    Buzatto, Adriana Zardini; de Oliveira Silva, Mariana; Poppi, Ronei Jesus; Simionato, Ana Valéria Colnaghi

    2017-05-01

    Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients. The concentrations of nucleosides in both groups were compared and a multivariate partial least squares-discriminant analysis classification model was optimized for prediction of prostate cancer. The validation of the model with an independent sample set resulted in the correct classification of 82.4% of the samples, with sensitivity of 90.5% and specificity of 76.7%. A significant downregulation of 5-methyluridine and inosine was observed, which can be indicative of the carcinogenic process. Therefore, such analytes are potential candidates for prostate cancer screening. Graphical Abstract Separation of the studied nucleosides and the internal standard 8-Bromoguanosine by CE-UV (a); classification of the external validation samples (30 from healthy volunteers and 21 from prostate cancer patients) by the developed Partial Least Square - Discriminant Analysis (PLS-DA) model with accuracy of 82.4% (b); Receiver Operating Characteristics (ROC) curve (c); and Variable Importance in the Projection (VIP) values for the studied nucleosides (d). A significant down-regulation of 5- methyluridine (5mU) and inosine (I) was observed, which can be indicative of the presence of prostate tumors.

  17. Na+-dependent nucleoside transport in liver: two different isoforms from the same gene family are expressed in liver cells.

    OpenAIRE

    Felipe, A; Valdes, R; Santo, B; Lloberas, J; Casado, J; Pastor-Anglada, M

    1998-01-01

    Hepatocytes show a Na+-dependent nucleoside transport activity that is kinetically heterogeneous and consistent with the expression of at least two independent concentrative Na+-coupled nucleoside transport systems (Mercader et al. Biochem. J. 317, 835-842, 1996). So far, only a single nucleoside carrier-related cDNA (SPNT) has been isolated from liver cells (Che et al. J. Biol. Chem. 270, 13596-13599, 1995). This cDNA presumably encodes a plasma membrane protein responsible for Na+-dependent...

  18. Crystal structure of bis[4-(1H-pyrrol-1-ylphenyl] ferrocene-1,1′-dicarboxylate: a potential chemotherapeutic drug

    Directory of Open Access Journals (Sweden)

    Wanda I. Pérez

    2015-05-01

    Full Text Available The title iron(II complex, [Fe(C16H12NO22], crystallizes in the orthorhombic space group Pbca with the Fe2+ cation positioned on an inversion center. The cyclopentadienyl (Cp rings adopt an anti conformation in contrast with other substituted ferrocenes in which the Cp rings appear in a nearly eclipsed conformation. The Cp and the aromatic rings are positioned out of the plane, with a twist angle of 70.20 (12°, and the C(Cp—C(CO bond length is shorter than a typical C—C single bond, which suggests a partial double-bond character and delocalization with the Cp π system. The structure of the complex is compared to other functionalized ferrocenes synthesized in our laboratory.

  19. Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

    OpenAIRE

    Maree, M. David; Neuse, Eberhard W.; Erasmus, Elizabeth; Swarts, Jannie C.

    2007-01-01

    The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymer...

  20. Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists

    Directory of Open Access Journals (Sweden)

    Gao Zhan-Guo

    2010-05-01

    Full Text Available Abstract Background Quantum dots (QDs are crystalline nanoparticles that are compatible with biological systems to provide a chemically and photochemically stable fluorescent label. New ligand probes with fluorescent reporter groups are needed for detection and characterization of G protein-coupled receptors (GPCRs. Results Synthetic strategies for coupling the A2A adenosine receptor (AR agonist CGS21680 (2-[4-(2-carboxyethylphenylethylamino]-5'-N-ethylcarboxamidoadenosine to functionalized QDs were explored. Conjugates tethered through amide-linked chains and poly(ethyleneglycol (PEG displayed low solubility and lacked receptor affinity. The anchor to the dendron was either through two thiol groups of (R-thioctic acid or through amide formation to a commercial carboxy-derivatized QD. The most effective approach was to use polyamidoamine (PAMAM D5 dendrons as multivalent spacer groups, grafted on the QD surface through a thioctic acid moiety. In radioligand binding assays, dendron nucleoside conjugate 11 displayed a moderate affinity at the human A2AAR (Kiapp 1.02 ± 0.15 μM. The QD conjugate of increased water solubility 13, resulting from the anchoring of this dendron derivative, interacted with the receptor with Kiapp of 118 ± 54 nM. The fluorescence emission of 13 occurred at 565 nm, and the presence of the pendant nucleoside did not appreciably quench the fluorescence. Conclusions This is a feasibility study to demonstrate a means of conjugating to a QD a small molecular pharmacophore of a GPCR that is relatively hydrophobic. Further enhancement of affinity by altering the pharmacophore or the linking structures will be needed to make useful affinity probes.

  1. Kinetic α-deuterium isotope effect as a probe of transition state structure and reaction mechanism in nucleoside hydrolysis

    International Nuclear Information System (INIS)

    Stein, R.L.

    1978-01-01

    Theoretical equilibrium α-deuterium isotope effects were calculated for systems modeling nucleoside and glycoside hydrolyses using a computer program (Burton, G.W., Sims, L.B., Wilson, J.C., and Fry, A.J., J. Amer. Chem. Soc., 99, 3374(1977)) which computes isotope effects directly from the expression of Biegeleisen and Mayer (Biegeleisen, J. and Mayer, M.G., J. Chem. Phys., 17, 675(1949)). For nucleoside hydrolysis proceeding through an oxocarbonium ion intermediate, KH/KD = 1.21 to 1.25; while for nucleoside hydrolysis proceeding through an oxocarbonium ion intermediate KH/KD = 1.15 to 1.19. The models used in the calculations were generated systematically and involved a minimum of subjectivity in the selection of molecular parameters. The isotope effects calculated formed the basis for the interpretation of experimental kinetic α-deuterium isotope effects for nucleoside and glycoside hydrolysis

  2. Cu{sub 2−x}S films as counter-electrodes for dye solar cells with ferrocene-based liquid electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Congiu, M., E-mail: mirko.congiu@fc.unesp.br [UNESP, Univ. Estadual Paulista, POSMAT — Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, Av. Eng. Luiz Edmundo Carrijo Coube14-01, 17033-360 Bauru, SP (Brazil); Nunes-Neto, O. [UNESP, Univ. Estadual Paulista, POSMAT — Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, Av. Eng. Luiz Edmundo Carrijo Coube14-01, 17033-360 Bauru, SP (Brazil); De Marco, M.L.; Dini, D. [University of Rome “La Sapienza”, Department of Chemistry, Piazzale Aldo Moro 5, Rome, RM (Italy); Graeff, C.F.O. [UNESP, Univ. Estadual Paulista, POSMAT — Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, Av. Eng. Luiz Edmundo Carrijo Coube14-01, 17033-360 Bauru, SP (Brazil); DC-FC, UNESP, Univ. Estadual Paulista, Av. Eng. Luiz Edmundo Carrijo Coube14-01, 17033-360 Bauru, SP (Brazil)

    2016-08-01

    In this work, the application of hexagonal CuS nanoparticle layers as counter electrodes for dye sensitized solar cells has been studied. A fast, cheap and reliable deposition method was proposed for the one-step preparation of Cu{sub 2−x}S layers on F-doped SnO{sub 2} within 30 min through an ink-based technique. The electrodes prepared with our method were tested with iodine/iodide electrolyte, Co(II)/(III) bipyridine redox shuttle and Fe(II)/(III) ferrocene-based liquid electrolyte. The Cu{sub 2−x}S layers showed high efficiency and stability with the ferrocene/ferrocenium redox couple, showing a fast charge recombination kinetic, low charge transfer resistance (R{sub ct} = 0.73 Ω cm{sup 2}), reasonably high limiting current (11.8 mA cm{sup −2}) and high stability in propylene carbonate. - Highlights: • We proposed a low-cost Cu{sub 2−x}S electrode for dye solar cells. • Easy deposition and processing • Suitable for large-area applications • Advantages and limitations of Cu{sub 2−x}S with three different redox electrolytes • High electro-catalytic efficiency and stability with the ferrocene/ferrocenium redox couple.

  3. Point mutations in a nucleoside transporter gene from Leishmania donovani confer drug resistance and alter substrate selectivity

    OpenAIRE

    Vasudevan, Gayatri; Ullman, Buddy; Landfear, Scott M.

    2001-01-01

    Leishmania parasites lack a purine biosynthetic pathway and depend on surface nucleoside and nucleobase transporters to provide them with host purines. Leishmania donovani possess two closely related genes that encode high affinity adenosine-pyrimidine nucleoside transporters LdNT1.1 and LdNT1.2 and that transport the toxic adenosine analog tubercidin in addition to the natural substrates. In this study, we have characterized a drug-resistant clonal mutant of L. do...

  4. Supplementation of Nucleosides During Selection can Reduce Sequence Variant Levels in CHO Cells Using GS/MSX Selection System.

    Science.gov (United States)

    Tang, Danming; Lam, Cynthia; Louie, Salina; Hoi, Kam Hon; Shaw, David; Yim, Mandy; Snedecor, Brad; Misaghi, Shahram

    2018-01-01

    In the process of generating stable monoclonal antibody (mAb) producing cell lines, reagents such as methotrexate (MTX) or methionine sulfoximine (MSX) are often used. However, using such selection reagent(s) increases the possibility of having higher occurrence of sequence variants in the expressed antibody molecules due to the effects of MTX or MSX on de novo nucleotide synthesis. Since MSX inhibits glutamine synthase (GS) and results in both amino acid and nucleoside starvation, it is questioned whether supplementing nucleosides into the media could lower sequence variant levels without affecting titer. The results show that the supplementation of nucleosides to the media during MSX selection decreased genomic DNA mutagenesis rates in the selected cells, probably by reducing nucleotide mis-incorporation into the DNA. Furthermore, addition of nucleosides enhance clone recovery post selection and does not affect antibody expression. It is further observed that nucleoside supplements lowered DNA mutagenesis rates only at the initial stage of the clone selection and do not have any effect on DNA mutagenesis rates after stable cell lines are established. Therefore, the data suggests that addition of nucleosides during early stages of MSX selection can lower sequence variant levels without affecting titer or clone stability in antibody expression. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes

    Directory of Open Access Journals (Sweden)

    G. Perrone

    2010-09-01

    Full Text Available The human equilibrative nucleoside transporter 1 (hENT1 is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively. Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036, while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.

  6. Can Crystal Symmetry and Packing Influence the Active Site Conformation of Homohexameric Purine Nucleoside Phosphorylases?

    Directory of Open Access Journals (Sweden)

    Marija Luić

    2016-06-01

    Full Text Available It is generaly believed that enzymes retain most of their functionality in the crystal form due to the large solvent content of protein crystals. This is facilitated by the fact that their natural environment in solution is not too far from the one found in the crystal form. Nevertheless, if the nature of the enzyme is such to require conformational changes, overcoming of the crystal packing constraints may prove to be too difficult. Such conformational change is present in one class of enzymes (purine nucleoside phosphorylases, that is the subject of our scientific interest for many years. The influence of crystal symmetry and crystal packing on the conformation of the active sites in the case of homohexameric purine nucleoside phosphorylases is presented and analysed. This work is licensed under a Creative Commons Attribution 4.0 International License.

  7. Three-dimensional structure of E. Coli purine nucleoside phosphorylase at 0.99 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Timofeev, V. I., E-mail: tostars@mail.ru [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation); Abramchik, Yu. A., E-mail: ugama@yandex.ru [Russian Academy of Sciences, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry (Russian Federation); Zhukhlistova, N. E., E-mail: inna@ns.crys.ras.ru [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation); Muravieva, T. I.; Esipov, R. S. [Russian Academy of Sciences, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry (Russian Federation); Kuranova, I. P. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2016-03-15

    Purine nucleoside phosphorylases (PNPs) catalyze the reversible phosphorolysis of nucleosides and are key enzymes involved in nucleotide metabolism. They are essential for normal cell function and can catalyze the transglycosylation. Crystals of E. coli PNP were grown in microgravity by the capillary counterdiffusion method through a gel layer. The three-dimensional structure of the enzyme was determined by the molecular-replacement method at 0.99 Å resolution. The structural features are considered, and the structure of E. coli PNP is compared with the structures of the free enzyme and its complexes with purine base derivatives established earlier. A comparison of the environment of the purine base in the complex of PNP with formycin A and of the pyrimidine base in the complex of uridine phosphorylase with thymidine revealed the main structural features of the base-binding sites. Coordinates of the atomic model determined with high accuracy were deposited in the Protein Data Bank (PDB-ID: 4RJ2).

  8. Understanding Food Labels

    Science.gov (United States)

    ... Healthy eating for girls Understanding food labels Understanding food labels There is lots of info on food ... need to avoid because of food allergies. Other food label terms top In addition to the Nutrition ...

  9. Mechanisms by Which Human DNA Primase Chooses To Polymerize a Nucleoside Triphosphate

    Czech Academy of Sciences Publication Activity Database

    Urban, M.; Joubert, Nicolas; Purse, B. W.; Hocek, Michal; Kuchta, R. D.

    2010-01-01

    Roč. 49, č. 4 (2010), s. 727-735 ISSN 0006-2960 R&D Projects: GA MŠk LC512; GA AV ČR IAA400550902 Grant - others:NIH(US) GM54194 Institutional research plan: CEZ:AV0Z40550506 Keywords : C-nucleosides * DNA polymerase * primase * mechanism Subject RIV: CC - Organic Chemistry Impact factor: 3.226, year: 2010

  10. Novel modified purine bases and nucleosides: new methodologies of synthesis and biological activity

    Czech Academy of Sciences Publication Activity Database

    Hocek, Michal

    -, č. 49 (2005), s. 29-30 ISSN 0261-3166. [International Symposium on Nucleic Acids Chemistry /4./. Fukuoka, 20.09.2005-22.09.2005] R&D Projects: GA ČR(CZ) GA203/03/0035; GA MŠk(CZ) 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : purines * nucleosides * synthesis Subject RIV: CC - Organic Chemistry

  11. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  12. Mechanism of action and selective toxicity of ascamycin, a nucleoside antibiotic.

    OpenAIRE

    Osada, H; Isono, K

    1985-01-01

    An unidentified Streptomyces sp. produces two nucleoside antibiotics, ascamycin and its dealanyl derivative. In contrast to the broad antibacterial activity of dealanylascamycin against various gram-negative and gram-positive bacteria, ascamycin showed selective toxicity against Xanthomonas citri and X. oryzae. Both ascamycin and dealanylascamycin inhibited the protein synthesis of X. citri, but only dealanylascamycin inhibited that of Escherichia coli. In cell-free systems from E. coli and X...

  13. Synthesis of alpha-Branched Acyclic Nucleoside Phosphonates as Potential Inhibitors of Bacterial Adenylate Cyclases

    Czech Academy of Sciences Publication Activity Database

    Frydrych, Jan; Skácel, Jan; Šmídková, Markéta; Mertlíková-Kaiserová, Helena; Dračínský, Martin; Gnanasekaran, Ramachandran; Lepšík, Martin; Soto-Velasquez, M.; Watts, V. J.; Janeba, Zlatko

    2018-01-01

    Roč. 13, č. 2 (2018), s. 199-206 ISSN 1860-7179 R&D Projects: GA MV VG20102015046; GA ČR(CZ) GBP208/12/G016; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * adenylate cyclase toxin * bisamidates * Bordetella pertussis * prodrugs Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.225, year: 2016

  14. Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

    Czech Academy of Sciences Publication Activity Database

    Eyer, L.; Šmídková, Markéta; Nencka, Radim; Neča, J.; Kastl, T.; Palus, Martin; De Clercq, E.; Růžek, Daniel

    2016-01-01

    Roč. 133, Sep (2016), s. 119-129 ISSN 0166-3542 R&D Projects: GA MZd(CZ) NV16-34238A; GA ČR(CZ) GA16-20054S Institutional support: RVO:61388963 ; RVO:60077344 Keywords : structure-activity relationship * tick-borne encephalitis * nucleoside inhibitor * antiviral activity * cytotoxicity Subject RIV: CC - Organic Chemistry; EE - Microbiology, Virology (BC-A) Impact factor: 4.271, year: 2016

  15. New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Dračínský, Martin; Snoeck, R.; Balzarini, J.; Pomeisl, Karel; Andrei, G.

    2017-01-01

    Roč. 25, č. 17 (2017), s. 4637-4648 ISSN 0968-0896 R&D Projects: GA ČR(CZ) GA14-00522S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * open-ring * PMEO-DAPy * 5-azacytosine * PME-azaC * HPMP-5-azaC Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.930, year: 2016

  16. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    International Nuclear Information System (INIS)

    Nanda, Dharmin; Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter; Vogels, Ronald; Havenga, Menzo; Driesse, Maarten; Avezaat, Cees; Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard; Smitt, Peter Sillevis

    2002-01-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-β-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of 123 I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with 123 I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). 123 I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with 123 I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after 123 I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with the transgene in the former E1

  17. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Dharmin [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands); Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter [Department of Nuclear Medicine, University Hospital Rotterdam (Netherlands); Vogels, Ronald; Havenga, Menzo [Crucell Holland BV, Leiden (Netherlands); Driesse, Maarten; Avezaat, Cees [Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Smitt, Peter Sillevis [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands)

    2002-07-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-{beta}-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of {sup 123}I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with {sup 123}I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). {sup 123}I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with {sup 123}I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after {sup 123}I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with

  18. Preliminary crystallographic studies of purine nucleoside phosphorylase from the cariogenic pathogen Streptococcus mutans

    International Nuclear Information System (INIS)

    Hou, Qiao-Ming; Liu, Xiang; Brostromer, Erik; Li, Lan-Fen; Su, Xiao-Dong

    2009-01-01

    Purine nucleoside phosphorylase (PNP), which is a pivotal enzyme in the nucleotide-salvage pathway, has been expressed in Escherichia coli strain BL21 (DE3) in a soluble form at a high level. After purification of the PNP enzyme, the protein was crystallized using the sitting-drop vapour-diffusion technique. The punA gene of the cariogenic pathogen Streptococcus mutans encodes purine nucleoside phosphorylase (PNP), which is a pivotal enzyme in the nucleotide-salvage pathway, catalyzing the phosphorolysis of purine nucleosides to generate purine bases and α-ribose 1-phosphate. In the present work, the PNP protein was expressed in Escherichia coli strain BL21 (DE3) in a soluble form at a high level. After purification of the PNP enzyme, the protein was crystallized using the sitting-drop vapour-diffusion technique; the crystals diffracted to 1.6 Å resolution at best. The crystals belonged to space group H3, with unit-cell parameters a = b = 113.0, c = 60.1 Å

  19. In Silico Investigation of Flavonoids as Potential Trypanosomal Nucleoside Hydrolase Inhibitors

    Directory of Open Access Journals (Sweden)

    Christina Hung Hung Ha

    2015-01-01

    Full Text Available Human African Trypanosomiasis is endemic to 37 countries of sub-Saharan Africa. It is caused by two related species of Trypanosoma brucei. Current therapies suffer from resistance and public accessibility of expensive medicines. Finding safer and effective therapies of natural origin is being extensively explored worldwide. Pentamidine is the only available therapy for inhibiting the P2 adenosine transporter involved in the purine salvage pathway of the trypanosomatids. The objective of the present study is to use computational studies for the investigation of the probable trypanocidal mechanism of flavonoids. Docking experiments were carried out on eight flavonoids of varying level of hydroxylation, namely, flavone, 5-hydroxyflavone, 7-hydroxyflavone, chrysin, apigenin, kaempferol, fisetin, and quercetin. Using AutoDock 4.2, these compounds were tested for their affinity towards inosine-adenosine-guanosine nucleoside hydrolase and the inosine-guanosine nucleoside hydrolase, the major enzymes of the purine salvage pathway. Our results showed that all of the eight tested flavonoids showed high affinities for both hydrolases (lowest free binding energy ranging from −10.23 to −7.14 kcal/mol. These compounds, especially the hydroxylated derivatives, could be further studied as potential inhibitors of the nucleoside hydrolases.

  20. [Comparative study on specific chromatograms and main nucleosides of cultivated and wild Cordyceps sinensis].

    Science.gov (United States)

    Zan, Ke; Huang, Li-Li; Guo, Li-Nong; Liu, Jie; Zheng, Jian; Ma, Shuang-Cheng; Qian, Zheng-Ming; Li, Wen-Jia

    2017-10-01

    This study is to establish the HPLC specific chromatogram and determine four main nucleosides of wild and cultivated Cordyceps sinensis. Uridine, inosine, guanosine and adenosine were selected as reference substance. HPLC analysis was performed on a Waters XSelect HSS T3 C₁₈ (4.6 mm×250 mm, 5 μm), with a mobile phase consisting of water(A)-acetonitrile (B) at a flow rate of 0.6 mL•min⁻¹ (0-5 min,0% B;5-15 min,0%-10% B, 15-30 min,10%-20% B, 30-33 min, 20%-50% B, 33-35 min, 50%-0% B, 35-40 min, 0% B). The detection wavelength was 260 nm and the column temperature was controlled at 30 ℃, and the injection volume was 5 μL. HPLC specific chromatogram of wild and cultivated C. sinensis was established and four main nucleosides were simultaneously determined by the above method. Specific chromatograms and contents of four main nucleosides showed no significant differences between cultivated and wild C. sinensis. These results can provide scientific evidences for further development and utilization of cultivated C. sinensis. Copyright© by the Chinese Pharmaceutical Association.

  1. Warm/cool-tone switchable thermochromic material for smart windows by orthogonally integrating properties of pillar[6]arene and ferrocene.

    Science.gov (United States)

    Wang, Sai; Xu, Zuqiang; Wang, Tingting; Xiao, Tangxin; Hu, Xiao-Yu; Shen, Ying-Zhong; Wang, Leyong

    2018-04-30

    Functional materials play a vital role in the fabrication of smart windows, which can provide a more comfortable indoor environment for humans to enjoy a better lifestyle. Traditional materials for smart windows tend to possess only a single functionality with the purpose of regulating the input of solar energy. However, different color tones also have great influences on human emotions. Herein, a strategy for orthogonal integration of different properties is proposed, namely the thermo-responsiveness of ethylene glycol-modified pillar[6]arene (EGP6) and the redox-induced reversible color switching of ferrocene/ferrocenium groups are orthogonally integrated into one system. This gives rise to a material with cooperative and non-interfering dual functions, featuring both thermochromism and warm/cool tone-switchability. Consequently, the obtained bifunctional material for fabricating smart windows can not only regulate the input of solar energy but also can provide a more comfortable color tone to improve the feelings and emotions of people in indoor environments.

  2. Electrochemical Sensor for Determination of Ascorbic Acid Using a 2-Chlorobenzoyl Ferrocene/Carbon Nanotube Paste Electrode

    Directory of Open Access Journals (Sweden)

    Sayed Zia Mohammadi

    2016-12-01

    Full Text Available A chemically modified carbon paste electrode with 2-chlorobenzoyl ferrocene (2CBF and carbon nanotube (2CBFCNPE was employed to study the electrocatalytic oxidation of ascorbic acid in aqueous solution using cyclic voltammetry, square wave voltammetry and chronoamperometry. The diffusion coefficient (D = 1.42 × 10-6 cm2 s-1, and the kinetic parameter such as the catalytic rate constant (k = 3.7 × 10 3 M-1 s-1 of ascorbic acid oxidation at the surface of 2CBFCNPE were determined using electrochemical approaches. It has been found that under an optimum condition (pH 4.0, the oxidation of ascorbic acid at the surface of such an electrode occurs at a potential about 85 mV less positive than that of an unmodified carbon paste electrode. Applying square wave voltammetry, in phosphate buffer solution (PBS of pH 4.0, the oxidation current increases linearly with two concentration intervals of ascorbic acid, one is 1.0 × 10-7-2.5 × 10-6 M and the other is 2.5 × 10-6-7.0 × 10-5 M. Detection limit (3δ was obtained 64.0 nM. This method was also examined for determination of ascorbic acid in some real samples.

  3. Mediation of glycosylated and partially-deglycosylated glucose oxidase of Aspergillus niger by a ferrocene-derivatised detergent.

    Science.gov (United States)

    Fraser, D M; Zakeeruddin, S M; Grätzel, M

    1992-01-30

    A ferrocene-derivatised detergent, (11-ferrocenylundecyl) trimethylammonium bromide (FTMAB), when oxidised to the corresponding ferricinium ion, was found by electrochemical studies to be an effective electron acceptor for reduced glucose oxidase of Aspergillus niger (EC 1.13.4) and thus acts as a electron-transfer mediator between glucose oxidase and a working electrode held at a potential sufficiently positive to reoxidise reduced FTMAB. An increase in mediating activity was produced when FTMAB was present in concentrations above its critical micelle concentration. An 'enzyme electrode' was formed by adsorption of glucose oxidase and FTMAB surfactant on a graphite rod. The electrode functioned as an amperometric biosensor for glucose in phosphate-buffered saline solution. A mixed micelle of glucose oxidase and FTMAB, probably adsorbed on the electrode surface, appears to be advantageous for the amperometric determination of glucose. Additionally, glucose oxidase was treated with alpha-mannosidase. When this partially-deglycosylated glucose oxidase was incorporated in an enzyme electrode, a 100-fold increase in the second-order rate constant (k) for electron transfer between the enzyme and FTMAB was observed, together with increased current densities, with respect to the equivalent values for FTMAB and commercial glucose oxidase. The use of deglycosylated enzymes in biosensors is suggested.

  4. The First Synthesis and Anti-retroviral Activity of 5',5'-Difluoro-3'-Hydroxy-Apiosyl Nucleoside Cyclomonophosphonic Acid Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seyeon; Hong, Joon Hee [Chosun University, Gwangju (Korea, Republic of)

    2016-04-15

    The first synthesis of novel 5',5'-difluoro-30-hydroxy apiose nucleoside cyclomonophosphonic acid analogs was performed as potent anti-retroviral agents. Phosphonation was performed by direct displacement of a triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding(α, α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside cyclomonophosphonic acid analogs. The synthesized nucleoside analogs were subjected to anti-viral screening against the human immunodeficiency virus-1 (HIV-1). Cytosine analogs show significant anti-HIV activity.

  5. Voltammetric analysis of 5-(4-Azidophenyl)-2 '-deoxycytidine nucleoside and azidophenyl-labelled single- and double-stranded DNAs

    Czech Academy of Sciences Publication Activity Database

    Daňhel, Aleš; Trošanová, Zuzana; Balintová, Jana; Havran, Luděk; Hocek, Michal; Barek, J.; Fojta, Miroslav

    2016-01-01

    Roč. 215, OCT2016 (2016), s. 72-83 ISSN 0013-4686 R&D Projects: GA ČR GBP206/12/G151 Institutional support: RVO:68081707 ; RVO:61388963 Keywords : Aromatic Azide * Enzymatic Incorporation * Mercury Electrode Subject RIV: BO - Biophysics; CC - Organic Chemistry (UOCHB-X) Impact factor: 4.798, year: 2016

  6. Synthesis of pyrimidinic nucleotides and nucleosides labelled with carbon 14, through tri-methylsilylated and lithiated derivatives

    International Nuclear Information System (INIS)

    Godbillon, Jacques

    1972-01-01

    After a presentation of the trimethysilylation, lithiation, and methylation processes, this research thesis reports the synthesis of methyl carbon 14 - 5 - uridine, of ethyl carbon 14 - 5 - desoxy - 2' - uridine, and of thymidine monophosphate - 5' (methyl carbon 14) by using silylated and lithiated derivatives. The author also reports preliminary studies of biological studies of the trimethylsilyl-5-uridine and of the iodine-6-thymine

  7. Issues in Data Labelling

    NARCIS (Netherlands)

    Cowie, Roddy; Cox, Cate; Martin, Jeam-Claude; Batliner, Anton; Heylen, Dirk K.J.; Karpouzis, Kostas; Cowie, Roddy; Pelachaud, Catherine; Petta, Paolo

    2011-01-01

    Labelling emotion databases is not a purely technical matter. It is bound up with theoretical issues. Different issues affect labelling of emotional content, labelling of the signs that convey emotion, and labelling of the relevant context. Linked to these are representational issues, involving time

  8. Mixed Map Labeling

    Directory of Open Access Journals (Sweden)

    Maarten Löffler

    2016-12-01

    Full Text Available Point feature map labeling is a geometric visualization problem, in which a set of input points must be labeled with a set of disjoint rectangles (the bounding boxes of the label texts. It is predominantly motivated by label placement in maps but it also has other visualization applications. Typically, labeling models either use internal labels, which must touch their feature point, or external (boundary labels, which are placed outside the input image and which are connected to their feature points by crossing-free leader lines. In this paper we study polynomial-time algorithms for maximizing the number of internal labels in a mixed labeling model that combines internal and external labels. The model requires that all leaders are parallel to a given orientation θ ∈ [0, 2π, the value of which influences the geometric properties and hence the running times of our algorithms.

  9. Quantification of the 2-deoxyribonolactone and nucleoside 5'-aldehyde products of 2-deoxyribose oxidation in DNA and cells by isotope-dilution gas chromatography mass spectrometry: differential effects of gamma-radiation and Fe2+-EDTA.

    Science.gov (United States)

    Chan, Wan; Chen, Bingzi; Wang, Lianrong; Taghizadeh, Koli; Demott, Michael S; Dedon, Peter C

    2010-05-05

    The oxidation of 2-deoxyribose in DNA has emerged as a critical determinant of the cellular toxicity of oxidative damage to DNA, with oxidation of each carbon producing a unique spectrum of electrophilic products. We have developed and validated an isotope-dilution gas chromatography-coupled mass spectrometry (GC-MS) method for the rigorous quantification of two major 2-deoxyribose oxidation products: the 2-deoxyribonolactone abasic site of 1'-oxidation and the nucleoside 5'-aldehyde of 5'-oxidation chemistry. The method entails elimination of these products as 5-methylene-2(5H)-furanone (5MF) and furfural, respectively, followed by derivatization with pentafluorophenylhydrazine (PFPH), addition of isotopically labeled PFPH derivatives as internal standards, extraction of the derivatives, and quantification by GC-MS analysis. The precision and accuracy of the method were validated with oligodeoxynucleotides containing the 2-deoxyribonolactone and nucleoside 5'-aldehyde lesions. Further, the well-defined 2-deoxyribose oxidation chemistry of the enediyne antibiotics, neocarzinostatin and calicheamicin gamma(1)(I), was exploited in control studies, with neocarzinostatin producing 10 2-deoxyribonolactone and 300 nucleoside 5'-aldehyde per 10(6) nt per microM in accord with its established minor 1'- and major 5'-oxidation chemistry. Calicheamicin unexpectedly caused 1'-oxidation at a low level of 10 2-deoxyribonolactone per 10(6) nt per microM in addition to the expected predominance of 5'-oxidation at 560 nucleoside 5'-aldehyde per 10(6) nt per microM. The two hydroxyl radical-mediated DNA oxidants, gamma-radiation and Fe(2+)-EDTA, produced nucleoside 5'-aldehyde at a frequency of 57 per 10(6) nt per Gy (G-value 74 nmol/J) and 3.5 per 10(6) nt per microM, respectively, which amounted to 40% and 35%, respectively, of total 2-deoxyribose oxidation as measured by a plasmid nicking assay. However, gamma-radiation and Fe(2+)-EDTA produced different proportions of 2

  10. A novel amperometric alcohol biosensor developed in a 3rd generation bioelectrode platform using peroxidase coupled ferrocene activated alcohol oxidase as biorecognition system.

    Science.gov (United States)

    Chinnadayyala, Somasekhar R; Kakoti, Ankana; Santhosh, Mallesh; Goswami, Pranab

    2014-05-15

    Alcohol oxidase (AOx) with a two-fold increase in efficiency (Kcat/Km) was achieved by physical entrapment of the activator ferrocene in the protein matrix through a simple microwave based partial unfolding technique and was used to develop a 3rd generation biosensor for improved detection of alcohol in liquid samples. The ferrocene molecules were stably entrapped in the AOx protein matrix in a molar ratio of ~3:1 through electrostatic interaction with the Trp residues involved in the functional activity of the enzyme as demonstrated by advanced analytical techniques. The sensor was fabricated by immobilizing ferrocene entrapped alcohol oxidase (FcAOx) and sol-gel chitosan film coated horseradish peroxidase (HRP) on a multi-walled carbon nanotube (MWCNT) modified glassy carbon electrode through layer-by-layer technique. The bioelectrode reactions involved the formation of H2O2 by FcAOx biocatalysis of substrate alcohol followed by HRP-catalyzed reduction of the liberated H2O2 through MWCNT supported direct electron transfer mechanism. The amperometric biosensor exhibited a linear response to alcohol in the range of 5.0 × 10(-6) to 30 × 10(-4)mol L(-1) with a detection limit of 2.3 × 10(-6) mol L(-1), and a sensitivity of 150 µA mM(-1) cm(-2). The biosensor response was steady for 28 successive measurements completed in a period of 5h and retained ~90% of the original response even after four weeks when stored at 4 °C. The biosensor was successfully applied for the determination of alcohol in commercial samples and its performance was validated by comparing with the data obtained by GC analyses of the samples. © 2013 Published by Elsevier B.V.

  11. Synthesis and application of aryl-ferrocenyl(pseudo-biarylic) complexes. Part 5. Design and synthesis of a new type of ferrocene-based planar chiral DMAP analogues. A new catalyst system for asymmetric nucleophilic catalysis

    DEFF Research Database (Denmark)

    Seitzberg, J.G; Dissing, C; Søtofte, Inger

    2005-01-01

    A new first-generation catalyst system for nucleophilic catalysis has been developed. It is based on a planar chiral ferrocene skeleton with either the potent nucleophile 4-(dimethylamino)pyridine (DMAP) or the related 4-nitropyridine N-oxide attached in either the 2- or the 3-position. The synth......A new first-generation catalyst system for nucleophilic catalysis has been developed. It is based on a planar chiral ferrocene skeleton with either the potent nucleophile 4-(dimethylamino)pyridine (DMAP) or the related 4-nitropyridine N-oxide attached in either the 2- or the 3-position...

  12. Ferrocene-based diradicals of imino nitroxide, nitronyl nitroxide and verdazyl, and their cations are possible SMM: A quantum chemical study

    Science.gov (United States)

    Pal, Arun K.; Datta, Sambhu N.

    2017-05-01

    Six diradicals designed from imino nitroxide, verdazyl and nitronyl nitroxide monoradicals coupled via the ferrocene moiety and six corresponding triradical cations are quantum chemically investigated. The transoid conformation is employed for considerations of general stability. All biradicals are found as very weakly and antiferromagnetically coupled. This agrees with experiment. The cations have strong antiferromagnetic spin-coupling. The charge and spin population distributions, spin alternation pattern, and the disjoint nature of SOMOs can be used to explain the nature and extent of magnetic interaction. Calculated EPR characteristics identify the neutral species as well as their cations as possible single molecule magnets.

  13. Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs

    Science.gov (United States)

    Saliba, Jason; Zabriskie, Ryan; Ghosh, Rajarshi; Powell, Bradford C; Hicks, Stephanie; Kimmel, Marek; Meng, Qingchang; Ritter, Deborah I; Wheeler, David A; Gibbs, Richard A; Tsai, Francis T F; Plon, Sharon E

    2016-01-01

    Background Mutations or alteration in expression of the 5’ nucleotidase gene family can confer altered responses to treatment with nucleoside analogs. While investigating leukemia susceptibility genes, we discovered a very rare p.L254P NT5C1A missense variant in the substrate recognition motif. Given the paucity of cellular drug response data from NT5C1A germline variation, we characterized p.L254P and eight rare variants of NT5C1A from genomic databases. Methods Through lentiviral infection, we created HEK293 cell lines that stably overexpress wildtype NT5C1A, p.L254P, or eight NT5C1A variants reported in the NHLBI Exome Variant server (one truncating and seven missense). IC50 values were determined by cytotoxicity assays after exposure to chemotherapeutic nucleoside analogs (Cladribine, Gemcitabine, 5-Fluorouracil). In addition, we used structure-based homology modeling to generate a 3D model for the C-terminal region of NT5C1A. Results The p.R180X (truncating), p.A214T, and p.L254P missense changes were the only variants that significantly impaired protein function across all nucleotide analogs tested (>5-fold difference versus WT; p<.05). Several of the remaining variants individually displayed differential effects (both more and less resistant) across the analogs tested. The homology model provided a structural framework to understand the impact of NT5C1A mutants on catalysis and drug processing. The model predicted active site residues within NT5C1A motif III and we experimentally confirmed that p.K314 (not p.K320) is required for NT5C1A activity. Conclusion We characterized germline variation and predicted protein structures of NT5C1A. Individual missense changes showed substantial variation in response to the different nucleoside analogs tested, which may impact patients’ responses to treatment. PMID:26906009

  14. Inhibitory effect of extracellular purine nucleotide and nucleoside concentrations on T cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Weiler, Monica [Department of Medicine III and Transfusion Medicine, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich (Germany); Schmetzer, Helga [Helmholtz Center Munich (Germany); German Research Center for Environmental Health, Munich (Germany); Braeu, Marion; Buhmann, Raymund [Helmholtz Center Munich (Germany); German Research Center for Environmental Health, Munich (Germany); Department of Medicine III and Transfusion Medicine, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich (Germany)

    2016-11-15

    The release of nucleic acids and derivatives after tissue-injury may affect cellular immune-response. We studied the impact of extracellular ribo-, desoxyribonucleotides and nucleosides on T-cell immunity. Peripheral-blood-mononuclear-cells (PBMCs) or isolated CD3{sup +}T-cells obtained from 6 healthy donors were stimulated via CD3/CD28 Dynabeads or dendritic cells (DCs) in the presence or absence of pyrimidine-, purine-nucleotides and -nucleosides (range 2–200 µM). Addition of deoxy-, guanosine-triphosphate (dGTP, GTP) and guanosine resulted concentration dependent in a complete, adenosine-triphosphate (ATP) in a partial inhibition of the induced T-cell-proliferation. Deoxyadenosine-triphosphate (dATP), adenosine and the pyrimidine-ribo- and -deoxyribonucleotides displayed no inhibitory capacity. Inhibitory effects of dGTP and GTP, but not of guanosine and ATP were culture-media-dependent and could be almost abrogated by use of the serum-free lymphocyte-culture-media X-Vivo15 instead of RPMI1640 with standard-supplementation. In contrast to RPMI1640, X-Vivo15 resulted in a significant down-regulation of the cell-surface-located ectonucleotidases CD39 (Ecto-Apyrase) and CD73 (Ecto-5′-Nucleotidase), critical for the extracellular nucleotides-hydrolysis to nucleosides, explaining the loss of inhibition mediated by dGTP and GTP, but not Guanosine. In line with previous findings ATP was found to exert immunosuppressive effects on T-cell-proliferation. Purine-nucleotides, dGTP and GTP displayed a higher inhibitory capacity, but seem to be strictly dependent on the microenvironmental conditions modulating the responsiveness of the respective T-lymphocytes. Further evaluation of experimental and respective clinical settings should anticipate these findings.

  15. Inhibitory effect of extracellular purine nucleotide and nucleoside concentrations on T cell proliferation

    International Nuclear Information System (INIS)

    Weiler, Monica; Schmetzer, Helga; Braeu, Marion; Buhmann, Raymund

    2016-01-01

    The release of nucleic acids and derivatives after tissue-injury may affect cellular immune-response. We studied the impact of extracellular ribo-, desoxyribonucleotides and nucleosides on T-cell immunity. Peripheral-blood-mononuclear-cells (PBMCs) or isolated CD3 + T-cells obtained from 6 healthy donors were stimulated via CD3/CD28 Dynabeads or dendritic cells (DCs) in the presence or absence of pyrimidine-, purine-nucleotides and -nucleosides (range 2–200 µM). Addition of deoxy-, guanosine-triphosphate (dGTP, GTP) and guanosine resulted concentration dependent in a complete, adenosine-triphosphate (ATP) in a partial inhibition of the induced T-cell-proliferation. Deoxyadenosine-triphosphate (dATP), adenosine and the pyrimidine-ribo- and -deoxyribonucleotides displayed no inhibitory capacity. Inhibitory effects of dGTP and GTP, but not of guanosine and ATP were culture-media-dependent and could be almost abrogated by use of the serum-free lymphocyte-culture-media X-Vivo15 instead of RPMI1640 with standard-supplementation. In contrast to RPMI1640, X-Vivo15 resulted in a significant down-regulation of the cell-surface-located ectonucleotidases CD39 (Ecto-Apyrase) and CD73 (Ecto-5′-Nucleotidase), critical for the extracellular nucleotides-hydrolysis to nucleosides, explaining the loss of inhibition mediated by dGTP and GTP, but not Guanosine. In line with previous findings ATP was found to exert immunosuppressive effects on T-cell-proliferation. Purine-nucleotides, dGTP and GTP displayed a higher inhibitory capacity, but seem to be strictly dependent on the microenvironmental conditions modulating the responsiveness of the respective T-lymphocytes. Further evaluation of experimental and respective clinical settings should anticipate these findings.

  16. Analysis of the Main Nucleosides in Cordyceps Sinensis by LC/ESI-MS

    Directory of Open Access Journals (Sweden)

    Yun-Biao He

    2010-01-01

    Full Text Available A sensitive, selective and reliable liquid chromatography-mass spectrometry coupled with electrospray ionization interface method for simultaneous separation and determination of thymine, adenine, adenosine and cordycepin in Cordyceps sinensis has been established. The optimum separation for these analytes was achieved using a gradient elution system and a 2.0 × 150 mm Shimadzu VP-ODS column. 2-Chloroadenosine was used as internal standard for this assay. [M+H]+ions at m/z 127, 136, 268, 252 and 302 were chosen and selective ion monitoring (SIM mode was used for quantitative analysis of the four main nucleosides. The regression equations were linear in the range of 1.0–117.5 μg·mL-1 for thymine, 1.8-127.0 μg·mL-1 for adenine, 0.6-114.0 μg·mL-1 for adenosine and 0.5-107.5 μg·mL-1 for cordycepin. The limits of quantitation (LOQ and detection (LOD were 1.0 and 0.2 μg·mL-1 for thymine, 1.8 and 0.6 μg·mL-1 for adenine, 0.6 and 0.1 μg·mL-1 for adenosine and 0.5 and 0.1 μg·mL-1 for cordycepin, respectively. The recoveries of the four nucleosides ranged from 98.47 to 99.32%. The developed method was successfully used to determine nucleosides in Cordyceps sinensis from different sources.

  17. The Crystal Structure of Streptococcus pyogenes Uridine Phosphorylase Reveals a Distinct Subfamily of Nucleoside Phosphorylases

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Timothy H.; Christoffersen, S.; Allan, Paula W.; Parker, William B.; Piskur, Jure; Serra, I.; Terreni, M.; Ealick, Steven E. (Cornell); (Pavia); (Lund); (Southern Research)

    2011-09-20

    Uridine phosphorylase (UP), a key enzyme in the pyrimidine salvage pathway, catalyzes the reversible phosphorolysis of uridine or 2'-deoxyuridine to uracil and ribose 1-phosphate or 2'-deoxyribose 1-phosphate. This enzyme belongs to the nucleoside phosphorylase I superfamily whose members show diverse specificity for nucleoside substrates. Phylogenetic analysis shows Streptococcus pyogenes uridine phosphorylase (SpUP) is found in a distinct branch of the pyrimidine subfamily of nucleoside phosphorylases. To further characterize SpUP, we determined the crystal structure in complex with the products, ribose 1-phosphate and uracil, at 1.8 {angstrom} resolution. Like Escherichia coli UP (EcUP), the biological unit of SpUP is a hexamer with an ?/? monomeric fold. A novel feature of the active site is the presence of His169, which structurally aligns with Arg168 of the EcUP structure. A second active site residue, Lys162, is not present in previously determined UP structures and interacts with O2 of uracil. Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is {approx}7-fold more efficient than SpUP. Biochemical studies of SpUP mutants showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that the negative charge in the transition state resides mostly on uracil O2. This is in contrast to EcUP for which transition state stabilization occurs mostly at O4.

  18. Absence of a Universal Mechanism of Mitochondrial Toxicity by Nucleoside Analogs▿

    Science.gov (United States)

    Lund, Kaleb C.; Peterson, LaRae L.; Wallace, Kendall B.

    2007-01-01

    Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 μM; 2.7 and 13.4 μg/ml), didanosine (ddI) (10 and 50 μM; 2.4 and 11.8 μg/ml), and zalcitabine (ddC) (1 and 5 μM; 0.21 and 1.1 μg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 μg/ml; 1.3 μM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 μM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard. PMID:17470651

  19. Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs.

    Science.gov (United States)

    Lund, Kaleb C; Peterson, LaRae L; Wallace, Kendall B

    2007-07-01

    Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 microM; 2.7 and 13.4 microg/ml), didanosine (ddI) (10 and 50 microM; 2.4 and 11.8 microg/ml), and zalcitabine (ddC) (1 and 5 microM; 0.21 and 1.1 microg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 microg/ml; 1.3 microM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 microM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard.

  20. Water-soluble ferrocene complexes (WFCs) functionalized silica nanospheres for WFC delivery in HepG2 tumor therapy.

    Science.gov (United States)

    Yan, Saisai; Hu, Fan; Hong, Xia; Shuai, Qi

    2018-09-01

    Silica-encapsulated nanospheres of water-soluble ferrocene complexes WFCs@SiO 2 and WFCs@SiO 2 @glutaraldehyde (GA) were first synthesized by a facile inverse-microemulsion method. The surface functional groups, particle size, and morphologies of nanospheres were characterized by IR spectra, UV-vis absorption spectra, dynamic light scattering (DLS) and SEM images. Single-crystal X-ray diffraction was used to confirm the molecular structure of free ferrocenyl-pyrazol ligand (L) and three WFCs, namely, [Ni(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 4 ] (5a), [Mg(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 4 ]·3H 2 O (5b), and [Ba(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 3 ] (5c). The electrochemical properties of 5a-5c were explored by cyclic voltammetry. The WFCs-loading capacities of 5a-5c in WFCs@SiO 2 were found to be 38.4, 38.2, and 38.1 μg/mg, respectively. Cell studies under two drug delivery modes (free diffusion and endocytosis) were carried out by MTT cell-survival assays and morphological observation of HepG2 cells. It's interesting that the cytotoxicity of WFCs against HepG2 was increased by applying silica nanocarriers. Compared to WFCs@SiO 2 , the modification of GA on the spherical surface provided not only the better water-dispersity but also additional functional groups for further modification of other pharmacophores. The novel nanocarrier system for WFC delivery present a novel concept-of-proof method to protect varieties of affordable metal-based anticancer agents in physiological conditions and provided experimental basis for future studies focusing on drug delivery of other WFCs. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Synthesis of Conformationally North-Locked Pyrimidine Nucleosides Built on an Oxabicyclo[3.1.0]hexane Scaffold | Center for Cancer Research

    Science.gov (United States)

    Beginning with a known 3-oxabicyclo[3.1.0]-hexane scaffold, the relocation of the fused cyclopropane ring bond and the shifting of the oxygen atom to an alternative location engendered a new 2-oxabicyclo[3.1.0]hexane template that mimics more closely the tetrahydrofuran ring of conventional nucleosides. The synthesis of this new class of locked nucleosides involved a novel

  2. Expression, purification, crystallization and preliminary X-ray analysis of a nucleoside kinase from the hyperthermophile Methanocaldococcus jannaschii

    International Nuclear Information System (INIS)

    Arnfors, Linda; Hansen, Thomas; Meining, Winfried; Schönheit, Peter; Ladenstein, Rudolf

    2005-01-01

    Nucleoside kinase from the hyperthermophilic archaeon M. jannaschii is a member of the PFK-B family which belongs to the ribokinase superfamily. Here, its expression, purification, crystallization and preliminary X-ray analysis are described. Methanocaldococcus jannaschii nucleoside kinase (MjNK) is an ATP-dependent non-allosteric phosphotransferase that shows high catalytic activity for guanosine, inosine and cytidine. MjNK is a member of the phosphofructokinase B family, but participates in the biosynthesis of nucleoside monophosphates rather than in glycolysis. MjNK was crystallized as the apoenzyme as well as in complex with an ATP analogue and Mg 2+ . The latter crystal form was also soaked with fructose-6-phosphate. Synchrotron-radiation data were collected to 1.70 Å for the apoenzyme crystals and 1.93 Å for the complex crystals. All crystals exhibit orthorhombic symmetry; however, the apoenzyme crystals contain one monomer per asymmetric unit whereas the complex crystals contain a dimer

  3. The identification and characterization of non-coding and coding RNAs and their modified nucleosides by mass spectrometry

    Science.gov (United States)

    Gaston, Kirk W; Limbach, Patrick A

    2014-01-01

    The analysis of ribonucleic acids (RNA) by mass spectrometry has been a valuable analytical approach for more than 25 years. In fact, mass spectrometry has become a method of choice for the analysis of modified nucleosides from RNA isolated out of biological samples. This review summarizes recent progress that has been made in both nucleoside and oligonucleotide mass spectral analysis. Applications of mass spectrometry in the identification, characterization and quantification of modified nucleosides are discussed. At the oligonucleotide level, advances in modern mass spectrometry approaches combined with the standard RNA modification mapping protocol enable the characterization of RNAs of varying lengths ranging from low molecular weight short interfering RNAs (siRNAs) to the extremely large 23 S rRNAs. New variations and improvements to this protocol are reviewed, including top-down strategies, as these developments now enable qualitative and quantitative measurements of RNA modification patterns in a variety of biological systems. PMID:25616408

  4. The identification and characterization of non-coding and coding RNAs and their modified nucleosides by mass spectrometry.

    Science.gov (United States)

    Gaston, Kirk W; Limbach, Patrick A

    2014-01-01

    The analysis of ribonucleic acids (RNA) by mass spectrometry has been a valuable analytical approach for more than 25 years. In fact, mass spectrometry has become a method of choice for the analysis of modified nucleosides from RNA isolated out of biological samples. This review summarizes recent progress that has been made in both nucleoside and oligonucleotide mass spectral analysis. Applications of mass spectrometry in the identification, characterization and quantification of modified nucleosides are discussed. At the oligonucleotide level, advances in modern mass spectrometry approaches combined with the standard RNA modification mapping protocol enable the characterization of RNAs of varying lengths ranging from low molecular weight short interfering RNAs (siRNAs) to the extremely large 23 S rRNAs. New variations and improvements to this protocol are reviewed, including top-down strategies, as these developments now enable qualitative and quantitative measurements of RNA modification patterns in a variety of biological systems.

  5. Enhancement of radiation-induced base release from nucleosides in alkaline solution: essential role of the O.- radical

    International Nuclear Information System (INIS)

    Scholes, M.L.; Schuchmann, M.N.; Sonntag, C. von

    1992-01-01

    The effect of pH on base release in the γ-radiolysis of N 2 O-saturated solutions of a number of nucleosides (including uridine, 3-methyluridine, 2', 3' -O-isopropylidene-uridine, and adenosine) has been investigated. For all these nucleosides, independent of the base or sugar moiety, base release is very low at pH below 10 (G∼(0.3-0.7) x 10 -7 mol J -1 ), but increases drastically to G∼(3-4) x 10 -7 mol J -1 at pH ≥ 13. It is concluded that the increase in base release at high pH is caused by the increasing participation of O .- , which, unlike . OH, attacks the nucleosides preferentially at their sugar moieties, and is not due to an OH - -induced radical transfer from the base to the sugar moiety. (author)

  6. Cu(I)-catalyzed efficient synthesis of 2′-Triazolo-nucleoside conjugates

    DEFF Research Database (Denmark)

    Mathur, D.; Rana, N.; Olsen, Carl Erik

    2015-01-01

    -nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of 1H NMR, 13C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier.......A small library of thirty-two 2′-triazolyl uridine and 2′-triazolyl-5-methyluridine has been synthesized by Cu(I)-catalyzed condensation of 2′-azido-2′-deoxyuridine and 2′-azido-2′-deoxy-5-methyluridine with different alkynes and aryl propargyl ethers in almost quantitative yields. Triazolo...

  7. Biophysical Insights into the Inhibitory Mechanism of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Nicolas Sluis-Cremer

    2013-11-01

    Full Text Available HIV-1 reverse transcriptase (RT plays a central role in HIV infection. Current United States Federal Drug Administration (USFDA-approved antiretroviral therapies can include one of five approved non-nucleoside RT inhibitors (NNRTIs, which are potent inhibitors of RT activity. Despite their crucial clinical role in treating and preventing HIV-1 infection, their mechanism of action remains elusive. In this review, we introduce RT and highlight major advances from experimental and computational biophysical experiments toward an understanding of RT function and the inhibitory mechanism(s of NNRTIs.

  8. Pyrimidine and nucleoside gamma-esters of L-Glu-Sar

    DEFF Research Database (Denmark)

    Eriksson, André H; Elm, Peter L; Begtrup, Mikael

    2005-01-01

    -tetrahydrofuran-3-yl ester)-Sar (I), l-Glu(thymine-1-yl-methyl ester)-Sar (II) and l-Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was studied in various aqueous and biological media. Affinity to and translocation via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown......The aim of the present study was to improve the synthetic pathway of bioreversible dipeptide derivatives as well as evaluate the potential of using l-Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and pyrimidine l-Glu-Sar derivatives. l-Glu(trans-2-thymine-1-yl...

  9. Template-directed addition of nucleosides to DNA by the BfiI restriction enzyme

    OpenAIRE

    Sasnauskas, Giedrius; Connolly, Bernard A.; Halford, Stephen E.; Siksnys, Virginijus

    2008-01-01

    Restriction endonucleases catalyse DNA cleavage at specific sites. The BfiI endonuclease cuts DNA to give staggered ends with 1-nt 3′-extensions. We show here that BfiI can also fill in the staggered ends: while cleaving DNA, it can add a 2′-deoxynucleoside to the reaction product to yield directly a blunt-ended DNA. We propose that nucleoside incorporation proceeds through a two-step reaction, in which BfiI first cleaves the DNA to make a covalent enzyme–DNA intermediate and then resolves it...

  10. Conformationally constrained nucleoside phosphonic acids - potent inhibitors of human mitochondrial and cytosolic 5'(3')-nucleotidases

    Czech Academy of Sciences Publication Activity Database

    Šimák, Ondřej; Pachl, Petr; Fábry, Milan; Buděšínský, Miloš; Jandušík, T.; Hnízda, Aleš; Skleničková, Radka; Petrová, Magdalena; Veverka, Václav; Řezáčová, Pavlína; Brynda, Jiří; Rosenberg, Ivan

    2014-01-01

    Roč. 12, č. 40 (2014), s. 7971-7982 ISSN 1477-0520 R&D Projects: GA ČR GA203/09/0820; GA ČR GA13-24880S; GA ČR GA13-26526S; GA MŠk(CZ) LK11205; GA AV ČR KAN200520801 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : 5'(3')-nucleotidase * structure * inhibition * cdN * mdN * nucleoside * SAR * phosphonic acid Subject RIV: CC - Organic Chemistry Impact factor: 3.562, year: 2014

  11. Synthesis and in vitro growth inhibitory activity of novel silyl- and trityl-modified nucleosides

    CSIR Research Space (South Africa)

    Panayides, Jenny-Lee

    2016-06-01

    Full Text Available -Farkas d, Hajierah Davids d,e , Leonie Harmse d , M. E. Christine Rey f , Ivan R. Green g, Stephen C. Pelly g, Robert Kiss c, Alexander Kornienko h, Willem A. L. van Otterlo a,g,⇑ a Molecular Sciences Institute, School of Chemistry, University..., Matieland 7602, South Africa hDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA Abstract Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating...

  12. Succesful labelling schemes

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Stacey, Julia

    2001-01-01

    . In the spring of 2001 MAPP carried out an extensive consumer study with special emphasis on the Nordic environmentally friendly label 'the swan'. The purpose was to find out how much consumers actually know and use various labelling schemes. 869 households were contacted and asked to fill in a questionnaire...... it into consideration when I go shopping. The respondent was asked to pick the most suitable answer, which described her use of each label. 29% - also called 'the labelling blind' - responded that they basically only knew the recycling label and the Government controlled organic label 'Ø-mærket'. Another segment of 6...

  13. Synthesizing labeled compounds

    International Nuclear Information System (INIS)

    London, R.E.; Matwiyoff, N.A.; Unkefer, C.J.; Walker, T.E.

    1983-01-01

    A metabolic study is presented of the chemical reactions provided by isotopic labeling and NMR spectroscopy. Synthesis of 13 C-labeled D-glucose, a 6-carbon sugar, involves adding a labeled nitrile group to the 5-carbon sugar D-arabinose by reaction with labeled hydrogen cyanide. The product of this reaction is then reduced and hydrolyzed to a mixture of the labeled sugars. The two sugars are separated by absorption chromotography. The synthesis of 13 C-labeled L-tyrosine, an amino acid, is also presented

  14. Quantitative assessment of the use of modified nucleoside triphosphates in expression profiling: differential effects on signal intensities and impacts on expression ratios

    Directory of Open Access Journals (Sweden)

    Dorris David

    2002-07-01

    Full Text Available Abstract Background The power of DNA microarrays derives from their ability to monitor the expression levels of many genes in parallel. One of the limitations of such powerful analytical tools is the inability to detect certain transcripts in the target sample because of artifacts caused by background noise or poor hybridization kinetics. The use of base-modified analogs of nucleoside triphosphates has been shown to increase complementary duplex stability in other applications, and here we attempted to enhance microarray hybridization signal across a wide range of sequences and expression levels by incorporating these nucleotides into labeled cRNA targets. Results RNA samples containing 2-aminoadenosine showed increases in signal intensity for a majority of the sequences. These results were similar, and additive, to those seen with an increase in the hybridization time. In contrast, 5-methyluridine and 5-methylcytidine decreased signal intensities. Hybridization specificity, as assessed by mismatch controls, was dependent on both target sequence and extent of substitution with the modified nucleotide. Concurrent incorporation of modified and unmodified ATP in a 1:1 ratio resulted in significantly greater numbers of above-threshold ratio calls across tissues, while preserving ratio integrity and reproducibility. Conclusions Incorporation of 2-aminoadenosine triphosphate into cRNA targets is a promising method for increasing signal detection in microarrays. Furthermore, this approach can be optimized to minimize impact on yield of amplified material and to increase the number of expression changes that can be detected.

  15. Purine Restriction Induces Pronounced Translational Upregulation of the NT1 Adenosine/Pyrimidine Nucleoside Transporter in Leishmania major

    OpenAIRE

    Ortiz, Diana; Valdés, Raquel; Sanchez, Marco A.; Hayenga, Johanna; Elya, Carolyn; Detke, Siegfried; Landfear, Scott M.

    2010-01-01

    Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gen...

  16. The Synthesis and Study of New Ribavirin Derivatives and Related Nucleoside Azole Carboxamides as Agents Active against RNA Viruses.

    Science.gov (United States)

    1981-09-01

    of the nitrate salt or degradation of the starting heterocycle. An alternate procedure for obtaining aromatic nitro compounds is the oxidation of the...SAcO OAc AcO OAc RO OR S102 99103, R-Ac 1--04, RC H -OH N HcO 0 cOY RO ᝹ HO O Ac RO OR 102 0_6 103, R - Ac 108, R = H 6- mercaptopurine riboside...occurring C-nucleoside antibiotic and unlike N-nucleosides, formycin B will not suffer enzymatic cleavage * 29 and degradation by phosphorolysis

  17. Electronic Submission of Labels

    Science.gov (United States)

    Pesticide registrants can provide draft and final labels to EPA electronically for our review as part of the pesticide registration process. The electronic submission of labels by registrants is voluntary but strongly encouraged.

  18. Robust Active Label Correction

    DEFF Research Database (Denmark)

    Kremer, Jan; Sha, Fei; Igel, Christian

    2018-01-01

    for the noisy data lead to different active label correction algorithms. If loss functions consider the label noise rates, these rates are estimated during learning, where importance weighting compensates for the sampling bias. We show empirically that viewing the true label as a latent variable and computing......Active label correction addresses the problem of learning from input data for which noisy labels are available (e.g., from imprecise measurements or crowd-sourcing) and each true label can be obtained at a significant cost (e.g., through additional measurements or human experts). To minimize......). To select labels for correction, we adopt the active learning strategy of maximizing the expected model change. We consider the change in regularized empirical risk functionals that use different pointwise loss functions for patterns with noisy and true labels, respectively. Different loss functions...

  19. Pesticide Product Label System

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Pesticide Product Label System (PPLS) provides a collection of pesticide product labels (Adobe PDF format) that have been approved by EPA under Section 3 of the...

  20. Semiotic labelled deductive systems

    Energy Technology Data Exchange (ETDEWEB)

    Nossum, R.T. [Imperial College of Science, Technology and Medicine, London (United Kingdom)

    1996-12-31

    We review the class of Semiotic Models put forward by Pospelov, as well as the Labelled Deductive Systems developed by Gabbay, and construct an embedding of Semiotic Models into Labelled Deductive Systems.

  1. Mental Labels and Tattoos

    Science.gov (United States)

    Hyatt, I. Ralph

    1977-01-01

    Discusses the ease with which mental labels become imprinted in our system, six basic axioms for maintaining negative mental tattoos, and psychological processes for eliminating mental tattoos and labels. (RK)

  2. Soil Fumigant Labels - Dazomet

    Science.gov (United States)

    Updated labels include new safety requirements for buffer zones and related measures. Find information from the Pesticide Product Labeling System (PPLS) for products such as Basamid G, manufactured by Amvac.

  3. Soil Fumigant Labels - Chloropicrin

    Science.gov (United States)

    Search by EPA registration number, product name, or company name, and follow the link to the Pesticide Product Label System (PPLS) for details on each fumigant. Updated labels include new safety requirements for buffer zones and related measures.

  4. Novel ferrocene-anchored ZnO nanoparticle/carbon nanotube assembly for glucose oxidase wiring: application to a glucose/air fuel cell.

    Science.gov (United States)

    Haddad, Raoudha; Mattei, Jean-Gabriel; Thery, Jessica; Auger, Aurélien

    2015-06-28

    Glucose oxidase (GOx) is immobilized on ZnO nanoparticle-modified electrodes. The immobilized glucose oxidase shows efficient mediated electron transfer with ZnO nanoparticles to which the ferrocenyl moiety is π-stacked into a supramolecular architecture. The constructed ZnO-Fc/CNT modified electrode exhibits high ferrocene surface coverage, preventing any leakage of the π-stacked ferrocene from the newly described ZnO hybrid nanoparticles. The use of the new architecture of ZnO supported electron mediators to shuttle electrons from the redox centre of the enzyme to the surface of the working electrode can effectively bring about successful glucose oxidation. These modified electrodes evaluated as a highly efficient architecture provide a catalytic current for glucose oxidation and are integrated in a specially designed glucose/air fuel cell prototype using a conventional platinum-carbon (Pt/C) cathode at physiological pH (7.0). The obtained architecture leads to a peak power density of 53 μW cm(-2) at 300 mV for the Nafion® based biofuel cell under "air breathing" conditions at room temperature.

  5. Convenient synthesis of magnetically recyclable Fe{sub 3}O{sub 4}@C@CdS photocatalysts by depositing CdS nanocrystals on carbonized ferrocene

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dan [Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China); Xie, Jianjian [Department of Materials Physics, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China); Zhang, Yong; Qiao, Ru [Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China); Li, Sheng [Department of Materials Physics, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China); Li, Zhengquan, E-mail: zqli@zjnu.edu.cn [Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China); Department of Materials Physics, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China)

    2015-10-15

    Development of magnetic visible-light-driven photocatalysts is desirable to the practical application of photocatalyts for collection and recycling use. Here we present a facile approach to synthesize Fe{sub 3}O{sub 4}@C@CdS magnetic photocatalysts which can avoid multi-step preparation process. Through one-step solvothermal carbonization of ferrocene, the produced carbon-coated Fe{sub 3}O{sub 4} clusters can serve as both magnetic cores and deposition substrates for in situ generating crystalline CdS nanocrystals on them by rapid microwave irradiation. The prepared Fe{sub 3}O{sub 4}@C@CdS nanoparticles exhibit a uniform core–shell structure and display good photocatalytic activity and recyclability in the degradation of organic dyes. These magnetic photocatalysts may find potential application in wastewater treatment for the future environment remedy. - Highlights: • A rapid strategy is presented to obtain multifunctional core–shell nanostructures. • Magnetic visible-light-driven Fe{sub 3}O{sub 4}@C@CdS nanophotocatalysts are synthesized. • Carbonized ferrocene can provide both magnetic cores and good deposition substrate. • Photocatalytic and recyclable properties of Fe{sub 3}O{sub 4}@C@CdS nanoparticles are explored.

  6. [Determination of 5 nucleosides components in culture of Paecilomyces hepialid by HPLC].

    Science.gov (United States)

    Yang, Dan; Ma, Yun-shu; Huang, Ting-ting; Chen, Cheng

    2015-08-01

    The concentration of 5 nucleosides, uracil, uridine, guanidine, adenine and adenosine in culture of Paecilomyces hepialid was determined by the developed method of HPLC. The HPLC method was performed on a Waters SunFire C18 (4.6 mm x 250 mm, 5 μm) column with methanol-water gradient elution as the mobile phase. The detection wavelength was 260 nm and the colunmn temperature was controlled at 30 °C. The linear range was 10.00-200.00 mg · L(-1) (r = 0.9994) for uracil, 10.10-202.00 mg · L(-1) (r = 0.9992) for uridine, 10.00-200.00 mg · L(-1) (r = 0.9991) for guanidine, 10.30-206.00 mg · L(-1) (r = 0.9992) for adenine and 10.45-209.00 mg · L(-1) (r = 0.9991) for adenosine, respectively. The RSD of precision was 0.032%, 0.035%, 0.039%, 0.049%, 0.00080%, respectively. The average recoveries of uracil, guanidine, adenine, and adenosine were 97.34%, 99.10%, 101.6%, 98.61% and 100.2% with RSD of 1.3%, 2.1%, 0.96%, 0.95%, and 1.3% respectively. The method showed high sensitivity, good selectivity, linearity and repeatability, which was suitable for the content analysis of 5 nucleosides components in P. hepialid and its extracts.

  7. Protein preparation, crystallization and preliminary X-ray analysis of Trypanosoma cruzi nucleoside diphosphate kinase 1

    International Nuclear Information System (INIS)

    Gómez Barroso, J. A.; Pereira, H.; Miranda, M.; Pereira, C.; Garratt, R. C.; Aguilar, C. F.

    2010-01-01

    T. cruzi TcNDPK1 was overexpressed in Escherichia coli as an N-terminally poly-His-tagged fusion protein and crystallized. The flagellated protozoan parasite Trypanosoma cruzi is the aetiological agent of Chagas disease. Nucleoside diphosphate kinases (NDPKs) are enzymes that are involved in energy management and nucleoside balance in the cell. T. cruzi TcNDPK1, a canonical isoform, was overexpressed in Escherichia coli as an N-terminally poly-His-tagged fusion protein and crystallized. Crystals grew after 72 h in 0.2 M MgCl 2 , 20% PEG 3350. Data were collected to 3.5 Å resolution using synchrotron X-ray radiation at the National Synchrotron Light Laboratory (Campinas, Brazil). The crystals belonged to the trigonal space group P3, with unit-cell parameters a = b = 127.84, c = 275.49 Å. Structure determination is under way and will provide relevant information that may lead to the first step in rational drug design for the treatment of Chagas disease

  8. Crystallization and preliminary X ray analysis of nucleoside diphosphate kinase 1 from T. cruzi

    International Nuclear Information System (INIS)

    Gomez Barroso, J.A.; Aguilar, C.F.; Miranda, M.R.; Pereira, C.A.

    2009-01-01

    Introduction: Trypanosoma cruzi is the etiologic agent of Chagas disease. The Nucleoside diphosphate kinases (NDPKs) are enzymes involved in energy management and nucleoside balance in the cell. T. cruzi TcNDPK1, a canonical isoform. The objective of this work is obtaining protein's crystals, diffract and process the data for tridimensional structure resolution. Materials and Methods: TcNDPK1 was expressed in E. coli as a fusion protein with Nterminal His-tag. TcNDPK1 was overexpressed and purified by FPLC. Crystallization was assayed by sitting drop and hanging drop vapor diffusion method. Crystals was frozen and diffracted on synchrotron x-ray radiation in Campinas (Brasil). The data set collected was reduced and merged using MOSFLM and SCALA programs. Results and Discussion: His-TcNDPK was overexpressed, purified and crystallized. The crystals are diffracted and collected the data to 3.5A. The crystals belong to the trigonal space group P3, with unit cell parameters a=127.94, b=127.84, c=275.49. Structure determination is under way. These results will provide relevant information that could be the first step in rational drug design for treating Chagas disease.(authors)

  9. Methylated nucleosides in tRNA and tRNA methyltransferases

    Directory of Open Access Journals (Sweden)

    Hiroyuki eHori

    2014-05-01

    Full Text Available To date, more than 90 modified nucleosides have been found in tRNA and the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s. Recent studies of the biosynthetic pathways have demonstrated that the availability of methyl group donors for the methylation in tRNA is important for correct and efficient protein synthesis. In this review, I focus on the methylated nucleosides and tRNA methyltransferases. The primary functions of tRNA methylations are linked to the different steps of protein synthesis, such as the stabilization of tRNA structure, reinforcement of the codon–anticodon interaction, regulation of wobble base pairing, and prevention of frameshift errors. However, beyond these basic functions, recent studies have demonstrated that tRNA methylations are also involved in the RNA quality control system and regulation of tRNA localization in the cell. In a thermophilic eubacterium, tRNA modifications and the modification enzymes form a network that responses to temperature changes. Furthermore, several modifications are involved in genetic diseases, infections, and the immune response. Moreover, structural, biochemical, and bioinformatics studies of tRNA methyltransferases have been clarifying the details of tRNA methyltransferases and have enabled these enzymes to be classified. In the final section, the evolution of modification enzymes is discussed.

  10. Identification of a nucleoside analog active against adenosine kinase–expressing plasma cell malignancies

    Science.gov (United States)

    Sadek, Jouliana; Hernandez-Hopkins, Denise; Akar, Gunkut; Barelli, Peter J.; Sahai, Michelle A.; Zhou, Hufeng; Totonchy, Jennifer; Jayabalan, David; Niesvizky, Ruben; Guasparri, Ilaria; Liu, Yifang; Sei, Shizuko; Shoemaker, Robert H.; Elemento, Olivier; Kaye, Kenneth M.

    2017-01-01

    Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI–sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers. PMID:28504647

  11. Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies.

    Science.gov (United States)

    Nayar, Utthara; Sadek, Jouliana; Reichel, Jonathan; Hernandez-Hopkins, Denise; Akar, Gunkut; Barelli, Peter J; Sahai, Michelle A; Zhou, Hufeng; Totonchy, Jennifer; Jayabalan, David; Niesvizky, Ruben; Guasparri, Ilaria; Hassane, Duane; Liu, Yifang; Sei, Shizuko; Shoemaker, Robert H; Warren, J David; Elemento, Olivier; Kaye, Kenneth M; Cesarman, Ethel

    2017-06-01

    Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.

  12. An Analysis of Enzyme Kinetics Data for Mitochondrial DNA Strand Termination by Nucleoside Reverse Transcription Inhibitors

    Science.gov (United States)

    Wendelsdorf, Katherine V.; Song, Zhuo; Cao, Yang; Samuels, David C.

    2009-01-01

    Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-γ hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-γ) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-γ with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication. PMID:19132079

  13. A Label to Regulate

    DEFF Research Database (Denmark)

    Tricoire, Aurélie; Boxenbaum, Eva; Laurent, Brice

    This paper examines the role labelling plays in the government of the contemporary economy.1Drawing on a detailed study of BBC-Effinergy, a French label for sustainable construction, we showhow the adoption and evolution of voluntary labels can be seen as emblematic of a governmentthrough experim...

  14. Labelling subway lines

    NARCIS (Netherlands)

    Garrido, M.A.; Iturriaga, C.; Márquez, A.; Portillo, J.R.; Reyes, P.; Wolff, A.; Eades, P.; Takaoka, T.

    2001-01-01

    Graphical features on map, charts, diagrams and graph drawings usually must be annotated with text labels in order to convey their meaning. In this paper we focus on a problem that arises when labeling schematized maps, e.g. for subway networks. We present algorithms for labeling points on a line

  15. Label Review Training: Module 1: Label Basics, Page 15

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the consequences of improper labeling.

  16. Label Review Training: Module 1: Label Basics, Page 23

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Lists types of labels that do not require review.

  17. Label Review Training: Module 1: Label Basics, Page 16

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about the importance of labels and the role in enforcement.

  18. Label Review Training: Module 1: Label Basics, Page 14

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about positive effects from proper labeling.

  19. Label Review Training: Module 1: Label Basics, Page 21

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about types of labels.

  20. Label Review Training: Module 1: Label Basics, Page 22

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about what labels require review.

  1. Label Review Training: Module 1: Label Basics, Page 18

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section discusses the types of labels.

  2. Label Review Training: Module 1: Label Basics, Page 26

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. Learn about mandatory and advisory label statements.

  3. Label Review Training: Module 1: Label Basics, Page 24

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is about which labels require review.

  4. Label Review Training: Module 1: Label Basics, Page 27

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See examples of mandatory and advisory label statements.

  5. Label Review Training: Module 1: Label Basics, Page 19

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This section covers supplemental distributor labeling.

  6. Label Review Training: Module 1: Label Basics, Page 17

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. See an overview of the importance of labels.

  7. Evaluation of nevirapine and/or hydroxyurea with nucleoside reverse transcriptase inhibitors in treatment-naive HIV-1-infected subjects

    NARCIS (Netherlands)

    Blanckenberg, Daniel H.; Wood, Robin; Horban, Andrzej; Beniowski, Marek; Boron-Kaczmarska, Anna; Trocha, Hanna; Halota, Waldemar; Schmidt, Reinhold E.; Fatkenheuer, G.; Jessen, Heiko; Lange, Joep M. A.

    2004-01-01

    Objective: To examine the effect of adding nevirapine (NVP) and/or hydroxyurea (HU) to a triple nucleoside analogue reverse transcriptase inhibitor (NRTI) regimen in terms of efficacy and tolerability. Methods: HIV-1-infected, treatment-naive adults were randomized, using a factorial design, to add

  8. The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind-Srogl cross-coupling reaction

    Czech Academy of Sciences Publication Activity Database

    Břehová, Petra; Česnek, Michal; Dračínský, Martin; Holý, Antonín; Janeba, Zlatko

    2011-01-01

    Roč. 67, č. 38 (2011), s. 7379-7385 ISSN 0040-4020 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : Liebeskind-Srogl cross - coupling * acyclic nucleoside phosphonates * pyrimidines * arylboronic acids * microwave Subject RIV: CC - Organic Chemistry Impact factor: 3.025, year: 2011

  9. Acyclic Nucleoside Phosphonates Containing 9-Deazahypoxanthine and a Five-Membered Heterocycle as Selective Inhibitors of Plasmodial 6-Oxopurine Phosphoribosyltransferases

    Czech Academy of Sciences Publication Activity Database

    Kaiser, Martin Maxmilian; Baszczyňski, Ondřej; Hocková, Dana; Poštová Slavětínská, Lenka; Dračínský, Martin; Keough, D. T.; Guddat, L. W.; Janeba, Zlatko

    2017-01-01

    Roč. 12, č. 14 (2017), s. 1133-1141 ISSN 1860-7179 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : inhibitors * nucleosides * malaria * phosphonates * purine salvage Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.225, year: 2016

  10. Synthesis and Evaluation of Novel Acyclic Nucleoside Phosphonates as Inhibitors of Plasmodium falciparum and Human 6-Oxopurine Phosphoribosyltransferases

    Czech Academy of Sciences Publication Activity Database

    Kaiser, Martin Maxmilian; Hocková, Dana; Wang, T. H.; Dračínský, Martin; Poštová Slavětínská, Lenka; Procházková, Eliška; Edstein, M. D.; Chavchich, M.; Keough, D. T.; Guddat, L. W.; Janeba, Zlatko

    2015-01-01

    Roč. 10, č. 10 (2015), s. 1707-1723 ISSN 1860-7179 R&D Projects: GA MV VG20102015046; GA ČR GAP207/11/0108 Institutional support: RVO:61388963 Keywords : 6-oxopurine * acyclic nucleoside phosphonates * phosphoribosyltransferases * malaria * phosphoramidates Subject RIV: CC - Organic Chemistry Impact factor: 2.980, year: 2015

  11. Pd-catalyzed versus uncatalyzed, PhI(OAc)2-mediated cyclization reactions of N6-([1,1'-biaryl]-2-yl)adenine nucleosides.

    Science.gov (United States)

    Satishkumar, Sakilam; Poudapally, Suresh; Vuram, Prasanna K; Gurram, Venkateshwarlu; Pottabathini, Narender; Sebastian, Dellamol; Yang, Lijia; Pradhan, Padmanava; Lakshman, Mahesh K

    2017-11-09

    In this work we have assessed reactions of N 6 -([1,1'-biaryl]-2-yl)adenine nucleosides with Pd(OAc) 2 and PhI(OAc) 2 , via a Pd II /Pd IV redox cycle. The substrates are readily obtained by Pd/Xantphos-catalyzed reaction of adenine nucleosides with 2-bromo-1,1'-biaryls. In PhMe, the N 6 -biarylyl nucleosides gave C6-carbazolyl nucleoside analogues by C-N bond formation with the exocyclic N 6 nitrogen atom. In the solvent screening for the Pd-catalyzed reactions, an uncatalyzed process was found to be operational. It was observed that the carbazolyl products could also be obtained in the absence of a metal catalyst by reaction with PhI(OAc) 2 in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Thus, under Pd catalysis and in HFIP, reactions proceed to provide carbazolyl nucleoside analogues, with some differences. If reactions of N 6 -biarylyl nucleoside substrates were conducted in MeCN, formation of aryl benzimidazopurinyl nucleoside derivatives was observed in many cases by C-N bond formation with the N 1 ring nitrogen atom of the purine (carbazole and benzimidazole isomers are readily separated by chromatography). Whereas Pd II /Pd IV redox is responsible for carbazole formation under the metal-catalyzed conditions, in HFIP and MeCN radical cations and/or nitrenium ions can be intermediates. An extensive set of radical inhibition experiments was conducted and the data are presented.

  12. Synthesis and applications of selectively {sup 13}C-labeled RNA

    Energy Technology Data Exchange (ETDEWEB)

    SantaLucia, J. Jr.; Shen, L.X.; Lewis, H.; Cai, Z.; Tinoci, I. Jr. [Univ. of California, Berkeley, CA (United States)

    1994-12-01

    Spectral overlap is a substantial problem in NMR studies of RNA molecules >30 nucleotides. To overcome this difficulty, we synthesized selectively {sup 13}C-labeled RNAs and adapted several isotope-edited two- and three-dimensional NMR experiments originally developed for protein studies. We optimized protocols for synthesis of multi-gram quantities of CTP, UTp, ATP, and GTP using a combination of synthetic organic and enzymatic methods. Uracil is prepared in 40 to 50% yield from {sup 13}C-cyanide in two steps. Using acetyl- tribenzoyl-ribose and standard chemistry uracil is then attached to the sugar (90% yield). The tribenzoyl-uridine intermediate is converted into uridine or cytidine quantitatively, depending on the deblocking protocol. Labeled purines are synthesized using simple pyrimidine precursors and reacting with {sup 13}C-formic acid (80% yield). Purine nucleosides are then synthesized using uridine phosphorylase and purine nucleoside phosphorylase. The nucleosides were converted to NMPs by treatment with POC1{sub 3} in triethylphosphate. We converted NMPs to NTPs by standard enzymatic methods. Selectively labeled RNAs were synthesized by run-off transcription using {sup 13}C-labeled NTPs. Several different strategies help solve over-lap problems in larger RNAs. Isotope-edited two-dimensional NMR experiments such as {omega}1-1/2 X-filtered NOESY simplify NMR spectra by dividing the normal NOESY spectrum into two subspectra-one involving NOEs from protons bound to {sup 12}C and one from protons bound to {sup 13}C. For example, we labeled A and U residues of a 34-nucleotide pseudoknot, and the {sup 12}C subspectrum of the 1/2 X-filtered NOESY contained NOEs only from G and C residues (along with adenine 2H); the {sup 13}C subspectrum contained NOEs only from A and U residues. Each subspectrum has less overlap than the NOESY of an unlabeled sample; the editing strategy allows each resonance to be identified by residue type (A, C, G, or U).

  13. Targeted Delivery of Deoxycytidine Kinase to Her2-Positive Cells Enhances the Efficacy of the Nucleoside Analog Fludarabine.

    Directory of Open Access Journals (Sweden)

    Sujatha P Koduvayur

    Full Text Available Cytotoxic drugs, such as nucleoside analogs and toxins, commonly suffer from off-target effects. One approach to mitigate this problem is to deliver the cytotoxic drug selectively to the intended site. While for toxins this can be achieved by conjugating the cell-killing moiety to a targeting moiety, it is not an option for nucleoside analogs, which rely on intracellular enzymes to convert them to their active triphosphorylated form. To overcome this limitation, and achieve site-targeted activation of nucleoside analogs, we fused the coding region of a prodrug-activating enzyme, deoxycytidine kinase (dCK, to affinity reagents that bind to the Her2 cell surface protein. We evaluated dCK fusions to an anti-Her2 affibody and Designed Ankyrin Repeat Protein (DARPin for their ability to kill cancer cells by promoting the activation of the nucleoside analog fludarabine. Cell staining and flow cytometry experiments with three Her2 positive cancer cell lines (BT-474-JB, JIMT-1 and SK-OV-3 indicate dCK fusions binding and cellular internalization. In contrast, these reagents bind only weakly to the Her2 negative cell line, MCF-7. Cell proliferation assays indicate that SK-OV-3 and BT-474-JB cell lines exhibit significantly reduced proliferation rates when treated with targeting-module fused dCK and fludarabine, compared to fludarabine alone. These findings demonstrate that we have succeeded in delivering active dCK into the Her2-positive cells, thereby increasing the activation of fludarabine, which ultimately reduces the dose of nucleoside analog needed for cell killing. This strategy may help establish the therapeutic index required to differentiate between healthy tissues and cancer cells.

  14. Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents

    Directory of Open Access Journals (Sweden)

    Pramod K. Sahu

    2017-07-01

    Full Text Available A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a exhibited the most potent anti-herpes simplex virus (HSV-1 (EC50 = 1.47 µM and HSV-2 (EC50 = 6.34 µM activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e–g exhibited significant anti-human cytomegalovirus (HCMV activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d.

  15. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Abstract Objective. Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged...... treatment with nucleoside or nucleotide analogs (NUCs) for CHB. Materials and methods. Patients with CHB and advanced fibrosis or cirrhosis prior to treatment with NUCs for at least 1 year were offered inclusion in the study. We measured liver stiffness using transient elastography (TE) at follow-up. TE cut...... duration was 50.5 months. Among patients with cirrhosis prior to treatment, 26 (49%) had liver stiffness below 11.0 kPa at follow-up, suggesting regression of cirrhosis. Among patients with advanced fibrosis (F3) prior to treatment, 10 (77%) had liver stiffness below 8.1 kPa after treatment, suggesting...

  16. A fluorescence study of the molecular interactions of harmane with the nucleobases, their nucleosides and mononucleotides.

    Science.gov (United States)

    Balón, M; Muñoz, M A; Carmona, C; Guardado, P; Galán, M

    1999-07-19

    Fluorescence binding studies of harmane to the elemental components of the nucleic acids were undertaken to investigate the origin of the interaction between the drug and DNA. Most of the tested substrates have been found to induce hypochromism in the absorption spectrum of harmane and to quench its fluorescence. The quenching process induced by the nucleobases and their nucleosides is mainly due to the formation of ground state 1:1 complexes. However, in the case of the mononucleotides a dynamic quenching component is also observed. This quenching component is likely due to the excited state interaction of harmane with the phosphate group of the nucleotides. UV-vis spectral changes and quenching measurements have been used to quantify the ground state association constants of the complexes and the quenching rate constants.

  17. Absence of a Universal Mechanism of Mitochondrial Toxicity by Nucleoside Analogs▿

    OpenAIRE

    Lund, Kaleb C.; Peterson, LaRae L.; Wallace, Kendall B.

    2007-01-01

    Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 μM; 2.7 and 13.4 μg/ml), didanosine (ddI) (10 and 50 μM; 2.4 and 11.8 μg/ml), and zalcitabine (ddC) (1 and 5 μM; 0.21 and 1.1 μg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. E...

  18. Cytological localization of adenosine kinase, nucleoside phosphorylase-1, and esterase-10 genes on mouse chromosome 14

    International Nuclear Information System (INIS)

    Samuelson, L.C.; Farber, R.A.

    1985-01-01

    The authors have determined the regional locations on mouse chromosome 14 of the genes for mouse adenosine kinase (ADK), nucleoside phosphorylase- 1 (NP-1), and esterase-10 (ES-10) by analysis of rearranged mouse chromosomes in gamma-irradiated Chinese hamster X mouse hybrid cell lines. Irradiated clones were screened for expression of the murine forms of these enzymes; segregant clones that expressed only one or two of the three markers were karyotyped. The patterns of enzyme expression in these segregants were correlated with the presence of rearranged chromosomes. The Adk gene was localized to bands A2 to B, Np-1 to bands B to C1, and Es-10 to bands D2 to E2

  19. Radiolysis of nucleosides in aqueous solutions: base liberation by the base attack mechanism

    International Nuclear Information System (INIS)

    Fujita, S.

    1984-01-01

    On the radiolysis of uridine and some other nucleosides in aqueous solution, a pH-dependent liberation of uracil or the corresponding base was found. e - sub(aq) and HOsup(anion radicals) 2 gave no freed bases, although many oxidizing radicals, including OH, Clsup(anion radicals) 2 , Brsup(anion radicals) 2 , (CNS)sup(anion radicals) 2 and SOsup(anion radicals) 4 , did cause the release of unaltered bases, depending on the pH of the solutions. The base yields were generally high at pH >= 11, with the exception of SOsup(anion radicals) 4 , which gave a rather high yield of uracil (from uridine) even in the pH region of - , present at high pH as the dissociated form of OH, may act partly as an oxidizing radical. A plausible mechanism of 3 1 -radical formation is discussed. (author)

  20. Labelling of equipment dispensers.

    Science.gov (United States)

    Gray, D C

    1993-01-01

    A new labelling system for use on medical equipment dispensers is tested. This system uses one of the objects stored in each unit of the dispenser as the 'label', by attaching it to the front of the dispenser with tape. The new system was compared to conventional written labelling by timing subjects asked to select items from two dispensers. The new system was 27% quicker than the conventional system. Images Fig. 1 PMID:8110335

  1. Deuterium labeled cannabinoids

    International Nuclear Information System (INIS)

    Driessen, R.A.

    1979-01-01

    Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

  2. The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication.

    Science.gov (United States)

    de Carvalho, Otavio Valério; Félix, Daniele Mendes; de Mendonça, Leila Rodrigues; de Araújo, Catarina Maria Cataldi Sabino; de Oliveira Franca, Rafael Freitas; Cordeiro, Marli Tenório; Silva Júnior, Abelardo; Pena, Lindomar José

    2017-12-01

    Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of disease caused by the virus. ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analogue derived from the prodrug azathioprine, against the epidemic ZIKV strain circulating in Brazil. In all of the assays, an epithelial (Vero) and a human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and effective concentrations of 6MMPr against ZIKV. Levels of ZIKV-RNA, viral infectious titre and the percentage of infected cells in the presence or absence of 6MMPr were used to determine antiviral efficacy. 6MMPr decreased ZIKV production by >99% in both cell lines in a dose- and time-dependent manner. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared with Vero cells, presenting a 50% cytotoxic concentrations (CC 50 ) of 460.3 µM and 291 µM, respectively. The selectivity index of 6MMPr for Vero and SH-SY5Y cells was 11.9 and 22.7, respectively, highlighting the safety profile of the drug to neuronal cells. Taken together, these results identify, for the first time, the thiopurine nucleoside analogue 6MMPr as a promising antiviral candidate against ZIKV that warrants further in vivo evaluation. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  3. Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides.

    Directory of Open Access Journals (Sweden)

    Eikan Mishima

    Full Text Available The biological roles of RNA modifications are still largely not understood. Thus, developing a method for detecting RNA modifications is important for further clarification. We developed a method for detecting RNA modifications called immuno-northern blotting (INB analysis and herein introduce its various capabilities. This method involves the separation of RNAs using either polyacrylamide or agarose gel electrophoresis, followed by transfer onto a nylon membrane and subsequent immunoblotting using antibodies against modified nucleosides for the detection of specific modifications. We confirmed that INB with the antibodies for 1-methyladenosine (m1A, N6-methyladenosine (m6A, pseudouridine, and 5-methylcytidine (m5C showed different modifications in a variety of RNAs from various species and organelles. INB with the anti-m5C antibody revealed that the antibody cross-reacted with another modification on DNA, suggesting the application of this method for characterization of the antibody for modified nucleosides. Additionally, using INB with the antibody for m1A, which is a highly specific modification in eukaryotic tRNA, we detected tRNA-derived fragments known as tiRNAs under the cellular stress response, suggesting the application for tracking target RNA containing specific modifications. INB with the anti-m6A antibody confirmed the demethylation of m6A by the specific demethylases fat mass and obesity-associated protein (FTO and ALKBH5, suggesting its application for quantifying target modifications in separated RNAs. Furthermore, INB demonstrated that the knockdown of FTO and ALKBH5 increased the m6A modification in small RNAs as well as in mRNA. The INB method has high specificity, sensitivity, and quantitative capability, and it can be employed with conventional experimental apparatus. Therefore, this method would be useful for research on RNA modifications and metabolism.

  4. Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides.

    Science.gov (United States)

    Mishima, Eikan; Jinno, Daisuke; Akiyama, Yasutoshi; Itoh, Kunihiko; Nankumo, Shinnosuke; Shima, Hisato; Kikuchi, Koichi; Takeuchi, Yoichi; Elkordy, Alaa; Suzuki, Takehiro; Niizuma, Kuniyasu; Ito, Sadayoshi; Tomioka, Yoshihisa; Abe, Takaaki

    2015-01-01

    The biological roles of RNA modifications are still largely not understood. Thus, developing a method for detecting RNA modifications is important for further clarification. We developed a method for detecting RNA modifications called immuno-northern blotting (INB) analysis and herein introduce its various capabilities. This method involves the separation of RNAs using either polyacrylamide or agarose gel electrophoresis, followed by transfer onto a nylon membrane and subsequent immunoblotting using antibodies against modified nucleosides for the detection of specific modifications. We confirmed that INB with the antibodies for 1-methyladenosine (m1A), N6-methyladenosine (m6A), pseudouridine, and 5-methylcytidine (m5C) showed different modifications in a variety of RNAs from various species and organelles. INB with the anti-m5C antibody revealed that the antibody cross-reacted with another modification on DNA, suggesting the application of this method for characterization of the antibody for modified nucleosides. Additionally, using INB with the antibody for m1A, which is a highly specific modification in eukaryotic tRNA, we detected tRNA-derived fragments known as tiRNAs under the cellular stress response, suggesting the application for tracking target RNA containing specific modifications. INB with the anti-m6A antibody confirmed the demethylation of m6A by the specific demethylases fat mass and obesity-associated protein (FTO) and ALKBH5, suggesting its application for quantifying target modifications in separated RNAs. Furthermore, INB demonstrated that the knockdown of FTO and ALKBH5 increased the m6A modification in small RNAs as well as in mRNA. The INB method has high specificity, sensitivity, and quantitative capability, and it can be employed with conventional experimental apparatus. Therefore, this method would be useful for research on RNA modifications and metabolism.

  5. The crystal structure of the hexameric purine nucleoside phosphorylase from Bacillus subtilis in complex with adenosine

    Energy Technology Data Exchange (ETDEWEB)

    Giuseppe, P.O.; Meza, A.N.; Martins, N.H.; Santos, C.R.; Murakami, M.T. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil)

    2012-07-01

    Full text: Purine nucleoside phosphorylases (PNPs) play a key role in the purine-salvage pathway in both prokaryotes and eukaryotes. Its ribosyltransferase activity is of great biotechnological interest due to potential application in the synthesis of nucleoside analogues used in the treatment of antiviral infections and in anticancer chemotherapy. Trimeric PNPs are found mainly in vertebrates and are specific for 6-oxo-purines whereas hexameric PNPs are prevalent in prokaryotes and exhibit a broad range of substrates including 6-oxo and 6-amino purines. BsPNP233, the hexameric PNP from B. subtilis, is able to catalyze the bioconversion of ribavirin, an anti-viral drug, and is relatively thermostable, being a good target for industrial use. Here we report the crystal structures of BsPNP233 in the apo form and in complex with adenosine solved at 2.65 and 1.91 resolution, respectively. The apo and ligand-bound BsPNP233 subunits superposed with an overall r.m.s. deviation of 0.31 for all C{alpha} atoms, which suggests that no major conformational changes occur upon substrate binding. Based on the crystal structure of BsPNP233 in complex with adenosine we have defined the active site residues implicated in binding the ribose (H4{sup *}, R43{sup *}, M64, R87, E178, M179, E180) and the nitrogenous base (S90, C91, G92, S202, V177, F159). These residues are highly conserved among the bacterial hexameric PNPs, suggesting they share the same mode of interaction with the substrates. This work will probably contribute to a better understanding of the molecular basis for the broad substrate specificity of hexameric PNPs and to projects aiming the rational design of PNPs for industrial purposes. (author)

  6. Aquaporin 3 (AQP3) participates in the cytotoxic response to nucleoside-derived drugs

    International Nuclear Information System (INIS)

    Pérez-Torras, Sandra; Casado, F Javier; Pastor-Anglada, Marçal

    2012-01-01

    Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite 5 ′ -deoxy-5-fluorouridine (5 ′ -DFUR) trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3) mRNA in cancer cells treated with 5 ′ -DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3 participates in the activity of genotoxic agents. The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches. 5 ′ -DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G 1 /S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU) also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced. Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest

  7. Effective sample labeling

    International Nuclear Information System (INIS)

    Rieger, J.T.; Bryce, R.W.

    1990-01-01

    Ground-water samples collected for hazardous-waste and radiological monitoring have come under strict regulatory and quality assurance requirements as a result of laws such as the Resource Conservation and Recovery Act. To comply with these laws, the labeling system used to identify environmental samples had to be upgraded to ensure proper handling and to protect collection personnel from exposure to sample contaminants and sample preservatives. The sample label now used as the Pacific Northwest Laboratory is a complete sample document. In the event other paperwork on a labeled sample were lost, the necessary information could be found on the label

  8. Ferrocene-Functionalized 4-(2,5-Di(thiophen-2-yl-1H-pyrrol-1-ylaniline: A Novel Design in Conducting Polymer-Based Electrochemical Biosensors

    Directory of Open Access Journals (Sweden)

    Rukiye Ayranci

    2015-01-01

    Full Text Available Herein, we report a novel ferrocenyldithiophosphonate functional conducting polymer and its use as an immobilization matrix in amperometric biosensor applications. Initially, 4-(2,5-di(thiophen-2-yl-1H-pyrrol-1-ylamidoferrocenyldithiophosphonate was synthesized and copolymerized with 4-(2,5-di(thiophen-2-yl-1H-pyrrol-1-ylbenzenamine at graphite electrodes. The amino groups on the polymer were utilized for covalent attachment of the enzyme glucose oxidase. Besides, ferrocene on the backbone was used as a redox mediator during the electrochemical measurements. Prior to the analytical characterization, optimization studies were carried out. The changes in current signals at +0.45 V were proportional to glucose concentration from 0.5 to 5.0 mM. Finally, the resulting biosensor was applied for glucose analysis in real samples and the data were compared with the spectrophotometric Trinder method.

  9. Dynamic map labeling.

    Science.gov (United States)

    Been, Ken; Daiches, Eli; Yap, Chee

    2006-01-01

    We address the problem of filtering, selecting and placing labels on a dynamic map, which is characterized by continuous zooming and panning capabilities. This consists of two interrelated issues. The first is to avoid label popping and other artifacts that cause confusion and interrupt navigation, and the second is to label at interactive speed. In most formulations the static map labeling problem is NP-hard, and a fast approximation might have O(nlogn) complexity. Even this is too slow during interaction, when the number of labels shown can be several orders of magnitude less than the number in the map. In this paper we introduce a set of desiderata for "consistent" dynamic map labeling, which has qualities desirable for navigation. We develop a new framework for dynamic labeling that achieves the desiderata and allows for fast interactive display by moving all of the selection and placement decisions into the preprocessing phase. This framework is general enough to accommodate a variety of selection and placement algorithms. It does not appear possible to achieve our desiderata using previous frameworks. Prior to this paper, there were no formal models of dynamic maps or of dynamic labels; our paper introduces both. We formulate a general optimization problem for dynamic map labeling and give a solution to a simple version of the problem. The simple version is based on label priorities and a versatile and intuitive class of dynamic label placements we call "invariant point placements". Despite these restrictions, our approach gives a useful and practical solution. Our implementation is incorporated into the G-Vis system which is a full-detail dynamic map of the continental USA. This demo is available through any browser.

  10. Construction and Characterization of a Chitosan-Immobilized-Enzyme and β-Cyclodextrin-Included-Ferrocene-Based Electrochemical Biosensor for H2O2 Detection

    Directory of Open Access Journals (Sweden)

    Wenbo Dong

    2017-07-01

    Full Text Available An electrochemical detection biosensor was prepared with the chitosan-immobilized-enzyme (CTS-CAT and β-cyclodextrin-included-ferrocene (β-CD-FE complex for the determination of H2O2. Ferrocene (FE was included in β-cyclodextrin (β-CD to increase its stability. The structure of the β-CD-FE was characterized. The inclusion amount, inclusion rate, and electrochemical properties of inclusion complexes were determined to optimize the reaction conditions for the inclusion. CTS-CAT was prepared by a step-by-step immobilization method, which overcame the disadvantages of the conventional preparation methods. The immobilization conditions were optimized to obtain the desired enzyme activity. CTS-CAT/β-CD-FE composite electrodes were prepared by compositing the CTS-CAT with the β-CD-FE complex on a glassy carbon electrode and used for the electrochemical detection of H2O2. It was found that the CTS-CAT could produce a strong reduction peak current in response to H2O2 and the β-CD-FE could amplify the current signal. The peak current exhibited a linear relationship with the H2O2 concentration in the range of 1.0 × 10−7–6.0 × 10−3 mol/L. Our work provided a novel method for the construction of electrochemical biosensors with a fast response, good stability, high sensitivity, and a wide linear response range based on the composite of chitosan and cyclodextrin.

  11. ELECTROCHEMISTRY CHARACTERIZATION OF FERROCENE ...

    African Journals Online (AJOL)

    2009-12-31

    Dec 31, 2009 ... the technique of cyclic voltammetry. The anodic (Epa) and the cathodic (Epc) peak potentials, as well as the corresponding anodic (ipa) and cathodic (ipc) peak currents, were obtained at different scan rates (0.05, 0.10, 0.30, 0.50 V.s-1). The diffusion coefficients. (D) have been calculated using the ...

  12. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  13. L-Aspartic and l-glutamic acid ester-based ProTides of anticancer nucleosides: Synthesis and antitumoral evaluation.

    Science.gov (United States)

    Gao, Ling-Jie; De Jonghe, Steven; Daelemans, Dirk; Herdewijn, Piet

    2016-05-01

    A series of novel aryloxyphosphoramidate nucleoside prodrugs based on l-aspartic acid and l-glutamic acid as amino acid motif has been synthesized and evaluated for antitumoral activity. Depending on the cancer cell line studied and on the nature of the parent nucleoside compound (gemcitabine, 5-iodo-2'-deoxy-uridine, floxuridine or brivudin), the corresponding ProTides are endowed with an improved or decreased cytotoxic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Edge colouring by total labellings

    DEFF Research Database (Denmark)

    Brandt, Stephan; Rautenbach, D.; Stiebitz, M.

    2010-01-01

    We introduce the concept of an edge-colouring total k-labelling. This is a labelling of the vertices and the edges of a graph G with labels 1, 2, ..., k such that the weights of the edges define a proper edge colouring of G. Here the weight of an edge is the sum of its label and the labels of its...

  15. Radioiodine and its labelled compounds

    International Nuclear Information System (INIS)

    Robles, Ana Maria

    1994-01-01

    Chemical characteristics and their nuclear characteristics, types of labelled molecules,labelling procedures, direct labelling with various oxidizing agents, indirect labelling with various conjugates attached to protein molecules, purification and quality control. Iodination damage.Safe handling of labelling procedures with iodine radioisotopes.Bibliography

  16. 'Naturemade' -- a new label

    International Nuclear Information System (INIS)

    Niederhaeusern, A.

    2001-01-01

    This short article discusses the introduction of the 'Naturemade' two-level labelling scheme in the Swiss electricity market, which is to help provide transparency in the market for green power and promote the building of facilities for its production. In the form of an interview with the CEO of Swissolar and the president of Greenpeace Switzerland, the pros and contras of these labels are discussed. In particular, the interview partners' opinions on the possible misuse of the less stringent label and the influence of the labels on the construction of new installations for the generation of electricity from renewable sources are presented. The basic principles of the promotional model behind the labels are listed

  17. Label Review Training: Module 1: Label Basics, Page 25

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review: clarity, accuracy, consistency with EPA policy, and enforceability.

  18. Label Review Training: Module 1: Label Basics, Page 29

    Science.gov (United States)

    This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is a quiz on Module 1.

  19. Cross-coupling reactions of unprotected halopurine bases, nucleosides, nucleotides and nucleoside triphosphates with 4-boronophenylalanine in water. Synthesis of (purin-8-yl)- and (purin-6-yl)phenylalanines

    Czech Academy of Sciences Publication Activity Database

    Čapek, Petr; Pohl, Radek; Hocek, Michal

    2006-01-01

    Roč. 4, č. 11 (2006), s. 2278-2284 ISSN 1477-0520 R&D Projects: GA AV ČR(CZ) 1QS400550501; GA MŠk(CZ) 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : amino acids * purines * nucleosides * cross-coupling reactions Subject RIV: CC - Organic Chemistry Impact factor: 2.874, year: 2006

  20. Purification, crystallization and preliminary X-ray diffraction study on pyrimidine nucleoside phosphorylase TTHA1771 from Thermus thermophilus HB8

    International Nuclear Information System (INIS)

    Shimizu, Katsumi; Kunishima, Naoki

    2007-01-01

    The pyrimidine nucleoside phosphorylase TTHA1771 from T. thermophilus HB8 has been overexpressed, purified and crystallized. The crystals diffract X-rays to 1.8 Å resolution using synchrotron radiation. Pyrimidine nucleoside phosphorylase (PYNP) catalyzes the reversible phosphorolysis of pyrimidines in the nucleotide-synthesis salvage pathway. In order to study the structure–thermostability relationship of this enzyme, PYNP from the extreme thermophile Thermus thermophilus HB8 (TTHA1771) has been cloned, overexpressed and purified. The TTHA1771 protein was crystallized at 291 K using the oil-microbatch method with PEG 4000 as a precipitant. A native data set was collected to 1.8 Å resolution using synchrotron radiation. The crystal belongs to the monoclinic space group P2 1 , with unit-cell parameters a = 58.83, b = 76.23, c = 103.86 Å, β = 91.3°

  1. Soil Fumigant Labels - Methyl Bromide

    Science.gov (United States)

    Search soil fumigant pesticide labels by EPA registration number, product name, or company, and follow the link to The Pesticide Product Label System (PPLS) for details. Updated labels include new safety requirements for buffer zones and related measures.

  2. Insights into phosphate cooperativity and influence of substrate modifications on binding and catalysis of hexameric purine nucleoside phosphorylases.

    Directory of Open Access Journals (Sweden)

    Priscila O de Giuseppe

    Full Text Available The hexameric purine nucleoside phosphorylase from Bacillus subtilis (BsPNP233 displays great potential to produce nucleoside analogues in industry and can be exploited in the development of new anti-tumor gene therapies. In order to provide structural basis for enzyme and substrates rational optimization, aiming at those applications, the present work shows a thorough and detailed structural description of the binding mode of substrates and nucleoside analogues to the active site of the hexameric BsPNP233. Here we report the crystal structure of BsPNP233 in the apo form and in complex with 11 ligands, including clinically relevant compounds. The crystal structure of six ligands (adenine, 2'deoxyguanosine, aciclovir, ganciclovir, 8-bromoguanosine, 6-chloroguanosine in complex with a hexameric PNP are presented for the first time. Our data showed that free bases adopt alternative conformations in the BsPNP233 active site and indicated that binding of the co-substrate (2'deoxyribose 1-phosphate might contribute for stabilizing the bases in a favorable orientation for catalysis. The BsPNP233-adenosine complex revealed that a hydrogen bond between the 5' hydroxyl group of adenosine and Arg(43* side chain contributes for the ribosyl radical to adopt an unusual C3'-endo conformation. The structures with 6-chloroguanosine and 8-bromoguanosine pointed out that the Cl(6 and Br(8 substrate modifications seem to be detrimental for catalysis and can be explored in the design of inhibitors for hexameric PNPs from pathogens. Our data also corroborated the competitive inhibition mechanism of hexameric PNPs by tubercidin and suggested that the acyclic nucleoside ganciclovir is a better inhibitor for hexameric PNPs than aciclovir. Furthermore, comparative structural analyses indicated that the replacement of Ser(90 by a threonine in the B. cereus hexameric adenosine phosphorylase (Thr(91 is responsible for the lack of negative cooperativity of phosphate binding

  3. Simple method for fast deprotection of nucleosides by triethylamine-catalyzed methanolysis of acetates in aqueous medium

    International Nuclear Information System (INIS)

    Meier, Lidiane; Monteiro, Gustavo C.; Baldissera, Rodrigo A.M.; Sa, Marcus Mandolesi

    2010-01-01

    A straightforward methodology for deacetylation of protected ribonucleosides was developed based on triethylamine-catalyzed solvolysis in aqueous methanol. Reactions are completed in a few minutes under microwave irradiation and the free nucleosides are obtained in high yield after simple evaporation of volatiles. Other important features include the involvement of readily available reagents and the compatibility with diverse functional groups, which make this process very attractive for broad application. (author)

  4. Acyclic nucleoside bisphosphonates: Synthesis and properties of chiral 2-amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines

    Czech Academy of Sciences Publication Activity Database

    Doláková, Petra; Dračínský, Martin; Masojídková, Milena; Šolínová, Veronika; Kašička, Václav; Holý, Antonín

    2009-01-01

    Roč. 44, č. 6 (2009), s. 2408-2424 ISSN 0223-5234 R&D Projects: GA MŠk 1M0508 Grant - others:NIH(US) 1UC1AIO62540-01 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * pyrimidine * bisphosphonates Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2009

  5. Sonogashira reactions of alpha and beta-1-ethynyl-2-deoxyribosides: synthesis of acetylene-extended C-nucleosides

    Czech Academy of Sciences Publication Activity Database

    Bobula, T.; Hocek, Michal; Kotora, M.

    2010-01-01

    Roč. 66, č. 2 (2010), s. 530-536 ISSN 0040-4020 R&D Projects: GA MŠk 1M0508; GA AV ČR IAA400550902 Institutional research plan: CEZ:AV0Z40550506 Keywords : alkynes * C-nucleosides * aryl halides * cross-coupling reactions Subject RIV: CC - Organic Chemistry Impact factor: 3.011, year: 2010

  6. Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals

    OpenAIRE

    Thess, Andreas; Grund, Stefanie; Mui, Barbara L; Hope, Michael J; Baumhof, Patrick; Fotin-Mleczek, Mariola; Schlake, Thomas

    2015-01-01

    Being a transient carrier of genetic information, mRNA could be a versatile, flexible, and safe means for protein therapies. While recent findings highlight the enormous therapeutic potential of mRNA, evidence that mRNA-based protein therapies are feasible beyond small animals such as mice is still lacking. Previous studies imply that mRNA therapeutics require chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system. Here we sh...

  7. Influence of Acyclic Nucleoside Phosphonate Antivirals on Gene Expression of Chemokine Receptors CCR5 and CXCR4

    Czech Academy of Sciences Publication Activity Database

    Potměšil, P.; Holý, Antonín; Zídek, Zdeněk

    2015-01-01

    Roč. 61, č. 1 (2015), s. 1-7 ISSN 0015-5500 R&D Projects: GA ČR GA305/03/1470; GA MŠk 1M0508 Institutional support: RVO:61388963 ; RVO:68378041 Keywords : acyclic nucleoside phosphonate * HIV * CCR5 * CXCR4 * cytokine * RT-PCR Subject RIV: CC - Organic Chemistry; FR - Pharmacology ; Medidal Chemistry (UEM-P) Impact factor: 0.833, year: 2015

  8. Direct One-Pot Synthesis of Nucleosides from Unprotected or 5-O-Monoprotected D-Ribose

    Czech Academy of Sciences Publication Activity Database

    Downey, Alan Michael; Richter, C.; Pohl, Radek; Mahrwald, R.; Hocek, Michal

    2015-01-01

    Roč. 17, č. 18 (2015), s. 4604-4607 ISSN 1523-7060 R&D Projects: GA ČR GAP207/11/0344 Institutional support: RVO:61388963 Keywords : nucleosides * cytostatics * biological activity Subject RIV: CC - Organic Chemistry Impact factor: 6.732, year: 2015 http://pubs.acs.org/doi/pdf/10.1021/acs.orglett.5b02332

  9. Enantiopurity analysis of new types of acyclic nucleoside phosphonates by capillary electrophoresis with cyclodextrins as chiral selectors

    Czech Academy of Sciences Publication Activity Database

    Šolínová, Veronika; Kaiser, Martin Maxmilian; Lukáč, Miloš; Janeba, Zlatko; Kašička, Václav

    2014-01-01

    Roč. 37, č. 3 (2014), s. 295-303 ISSN 1615-9306 R&D Projects: GA ČR(CZ) GAP206/12/0453; GA ČR(CZ) GA13-17224S; GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * CE * chiral analysis * cyclodextrins * nucleotide analogs Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.737, year: 2014

  10. Distinct modulation of telomere length in two T-lymphoblastic leukemia cell lines by cytotoxic nucleoside phosphonates PMEG and PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Hájek, Miroslav; Cvilink, Viktor; Votruba, Ivan; Holý, Antonín; Mertlíková-Kaiserová, Helena

    2010-01-01

    Roč. 643, č. 1 (2010), s. 6-12 ISSN 0014-2999 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * PMEG * PMEDAP * telomere length * telomerase inhibition Subject RIV: CC - Organic Chemistry Impact factor: 2.737, year: 2010

  11. Design and synthesis of N₁-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors.

    Science.gov (United States)

    Monforte, Anna-Maria; Ferro, Stefania; De Luca, Laura; Lo Surdo, Giuseppa; Morreale, Francesca; Pannecouque, Christophe; Balzarini, Jan; Chimirri, Alba

    2014-02-15

    A series of novel N1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Estimation of apparent binding constant of complexes of selected acyclic nucleoside phosphonates with beta-cyclodextrin by affinity capillary electrophoresis

    Czech Academy of Sciences Publication Activity Database

    Šolínová, Veronika; Mikysková, Hana; Kaiser, Martin Maxmilian; Janeba, Zlatko; Holý, Antonín; Kašička, Václav

    2016-01-01

    Roč. 37, č. 2 (2016), s. 239-247 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA13-17224S; GA ČR(CZ) GA15-01948S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * affinity capillary electrophoresis * binding constant * nucleotide analogs * beta-cyclodextrin Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 2.744, year: 2016

  13. Nucleoside adducts are formed by cooperative reaction of acetaldehyde and alcohols: Possible mechanism for the role of ethanol in carcinogenesis

    International Nuclear Information System (INIS)

    Fraenkel-Conrat, H.; Singer, B.

    1988-01-01

    The exocyclic amino groups of ribonucleosides and deoxyribonucleosides react rapidly at ambient temperature with acetaldehyde and alcohols to yield mixed acetals [-NH-CH(CH 3 )OR]. Nucleotides and nucleoside di- and triphosphates also react. Depending on the nucleoside used and on the relative amounts of aldehyde, alcohol, and water, preparative reactions reach equilibrium with yields up to 75% in a few house. The structures have been confirmed by fast atom bombardment MS and proton NMR. Half-lives at 37 degree C have been determined, and maximum stability is in the pH range of 7.5-9.5. In the absence of alcohol, acetaldehyde-nucleoside adducts could be isolated at 4 degree C, but these were too unstable to characterize except for their UV spectra, also at 4 degree C. Ethanol is often present in human blood and tissues, and acetaldehyde is its initial metabolic product, as well as being formed by many other metabolic processes. Both chemicals have separately been implicated in carcinogenic and other cytophathologic processes, but no cooperative mechanism has been proposed. The reactions reported here are of biological concern because they also occur in dilute aqueous solution. These finding supply a mechanism by which ethanol can be covalently bound to nucleic acids under physiological conditions

  14. Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.

    Science.gov (United States)

    Daniels, Geoff; Ballif, Bryan A; Helias, Virginie; Saison, Carole; Grimsley, Shane; Mannessier, Lucienne; Hustinx, Hein; Lee, Edmond; Cartron, Jean-Pierre; Peyrard, Thierry; Arnaud, Lionel

    2015-06-04

    The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible for the At(a-) blood type. The resulting p.Glu391Lys variation in the last extracellular loop of the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its ability to transport nucleosides and nucleoside analog drugs. Furthermore, we identified 3 individuals of European ancestry who are homozygous for a null mutation in SLC29A1 (c.589+1G>C) and thus have the Augustine-null blood type. These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently suggested by the skeletal phenotype of aging Slc29a1(-/-) mice. Our results establish Augustine as a new blood group system and place SLC29A1 as a new candidate gene for idiopathic disorders characterized with ectopic calcification/mineralization. © 2015 by The American Society of Hematology.

  15. Radioactive labelled orgotein

    International Nuclear Information System (INIS)

    1980-01-01

    The preparation and use of radioactively labelled orgotein, i.e. water-soluble protein congeners in pure, injectable form, is described. This radiopharmaceutical is useful in scintigraphy, especially for visualization of the kidneys where the orgotein is rapidly concentrated. Details of the processes for labelling bovine orgotein with sup(99m)Tc, 60 Co, 125 I or 131 I are specified. The pharmaceutical preparation of the labelled orgotein for intravenous and parenteral administration is also described. Examples using either sup(99m)TC or 125 I-orgotein in scintiscanning dogs' kidneys are given. (UK)

  16. On Online Labeling with Polynomially Many Labels

    DEFF Research Database (Denmark)

    Babka, Martin; Bulánek, Jan; Cunat, Vladimír

    2012-01-01

    be necessary to change the labels of some items; such changes may be done at any time at unit cost for each change. The goal is to minimize the total cost. An alternative formulation of this problem is the file maintenance problem, in which the items, instead of being labeled, are maintained in sorted order...... in an array of length m, and we pay unit cost for moving an item. For the case m = cn for constant c > 1, there are known algorithms that use at most O(n log(n)2) relabelings in total [9], and it was shown recently that this is asymptotically optimal [1]. For the case of m = θ(nC) for C > 1, algorithms...

  17. Determination of nucleosides in Cordyceps sinensis and Ganoderma lucidum by high performance liquid chromatography method

    Directory of Open Access Journals (Sweden)

    Masood Shah Khan

    2015-01-01

    Full Text Available Background: Nucleosides are supportive in the regulation and modulation of various physiological processes in body, they acts as precursors in nucleic acid synthesis, enhance immune response, help in absorption of iron and influence the metabolism of fatty acids. Cordyceps sinensis and Ganoderma lucidum are well-known for its use in traditional medicine of China, Nepal and India. They are rich in nucleosides such as adenine, adenosine, cordycepin, etc. Hence, a simple, economic and accurate high-performance liquid chromatography (HPLC analytical method was proposed for determination of adenine and adenosine for the quality control of plants. Materials and Methods: Chromatographic experiments were conducted on YL9100 HPLC system (South Korea. Reversed-phase chromatography was performed on a C18 column with methanol and dihydrogen phosphate as the mobile phase in isocratic elution method at a flow rate of 1.0 mL/min. Detection was carried out at 254 nm, which gives a sharp peak of adenine and adenosine at a retention time of 6.53 ± 0.02 min and 12.41 ± 0.02, respectively. Results and Discussion: Linear regression analysis data for the calibration plot showed a good linear relationship between response and concentration in the range of 25–200 µg/mL for adenosine and 100–800 µg/mL for adenine with regression coefficient of 0.999 and 0.996, respectively. The adenine was found 0.16% and 0.71% w/w in G. lucidum and in C. sinensis, respectively, and adenosine was found to be 0.14% w/w in G. lucidum whereas absent in C. sinensis. Conclusion: The developed HPLC method for the quantification of adenosine and adenine can be used for the quality control and standardization of crude drug and for the different herbal formulations, in which adenine and adenosine are present as major constituents. The wide linearity range, sensitivity, accuracy, and simple mobile phase imply the method is suitable for routine quantification of adenosine and adenine with

  18. Clinical applications of cells labelling

    International Nuclear Information System (INIS)

    Gonzalez, B.M.

    1994-01-01

    Blood cells labelled with radionuclides are reviewed and main applications are described. Red blood cell labelling by both random and specific principle. A table with most important clinical uses, 99mTc labelling of RBC are described pre tinning and in vivo reduction of Tc, in vitro labelling and administration of labelled RBC and in vivo modified technique. Labelled leucocytes with several 99mTc-complex radiopharmaceuticals by in vitro technique and specific monoclonal s for white cells(neutrofiles). Labelled platelets for clinical use and research by in vitro technique and in vivo labelling

  19. C-C bond unsaturation degree in monosubstituted ferrocenes for molecular electronics investigated by a combined near-edge x-ray absorption fine structure, x-ray photoemission spectroscopy, and density functional theory approach

    International Nuclear Information System (INIS)

    Boccia, A.; Lanzilotto, V.; Marrani, A. G.; Zanoni, R.; Stranges, S.; Alagia, M.; Fronzoni, G.; Decleva, P.

    2012-01-01

    We present the results of an experimental and theoretical investigation of monosubstituted ethyl-, vinyl-, and ethynyl-ferrocene (EtFC, VFC, and EFC) free molecules, obtained by means of synchrotron-radiation based C 1s photoabsorption (NEXAFS) and photoemission (C 1s XPS) spectroscopies, and density functional theory (DFT) calculations. Such a combined study is aimed at elucidating the role played by the C-C bond unsaturation degree of the substituent on the electronic structure of the ferrocene derivatives. Such substituents are required for molecular chemical anchoring onto relevant surfaces when ferrocenes are used for molecular electronics hybrid devices. The high resolution C 1s NEXAFS spectra exhibit distinctive features that depend on the degree of unsaturation of the hydrocarbon substituent. The theoretical approach to consider the NEXAFS spectrum made of three parts allowed to disentangle the specific contribution of the substituent group to the experimental spectrum as a function of its unsaturation degree. C 1s IEs were derived from the experimental data analysis based on the DFT calculated IE values for the different carbon atoms of the substituent and cyclopentadienyl (Cp) rings. Distinctive trends of chemical shifts were observed for the substituent carbon atoms and the substituted atom of the Cp ring along the series of ferrocenes. The calculated IE pattern was rationalized in terms of initial and final state effects influencing the IE value, with special regard to the different mechanism of electron conjugation between the Cp ring and the substituent, namely the σ/π hyperconjugation in EtFC and the π-conjugation in VFC and EFC.

  20. FDA Online Label Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The drug labels and other drug-specific information on this Web site represent the most recent drug listing information companies have submitted to the Food and Drug...

  1. Figuring Out Food Labels

    Science.gov (United States)

    ... It's also displayed in grocery stores near fresh foods, like fruits, vegetables, and fish. The nutrition facts label includes: a ... found in citrus fruits, other fruits, and some vegetables. Food companies might also list the amounts of other ...

  2. Energy efficiency labelling

    Energy Technology Data Exchange (ETDEWEB)

    1978-04-01

    This research assesses the likely effects on UK consumers of the proposed EEC energy-efficiency labeling scheme. Unless (or until) an energy-labeling scheme is introduced, it is impossible to do more than postulate its likely effects on consumer behavior. This report shows that there are indeed significant differences in energy consumption between different brands and models of the same appliance of which consumers are unaware. Further, the report suggests that, if a readily intelligible energy-labeling scheme were introduced, it would provide useful information that consumers currently lack; and that, if this information were successfully presented, it would be used and could have substantial effects in reducing domestic fuel consumption. Therefore, it is recommended that an energy labeling scheme be introduced.

  3. Like your labels?

    Science.gov (United States)

    Field, Michele

    2010-01-01

    The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off.

  4. Labelling of electricity

    International Nuclear Information System (INIS)

    Dettli, R.; Markard, J.

    2001-01-01

    This comprehensive report for the Swiss Federal Office of Energy (SFOE) presents a possible course of action to be taken to provide a means of declaring the sources of electrical power, as is foreseen in the draft of new Swiss electricity market legislation. The report presents the basic ideas behind the idea and defines the terms used such as labelling, certificates and declarations. Also, the legal situation in the European Union and in Switzerland is examined and a quantitative overview of electricity production and consumption is presented. Suggestions for a labelling scheme are made and some of the problems to be expected are looked at. The report also presents a series of examples of labelling schemes already implemented in other countries, such as Austria, Great Britain, Sweden and Germany. Tradable certificates and tracking systems are discussed as are initial quality labels like the Swiss 'Naturemade' label for green power. A concrete recommendation for the declaration and labelling of electricity in Switzerland is presented and various factors to be considered such as import/export, pumped storage, distribution losses, small-scale producers as well as the time-scales for introduction are discussed

  5. 78 FR 66826 - Prior Label Approval System: Generic Label Approval

    Science.gov (United States)

    2013-11-07

    ... raising of animals, such as ``no antibiotics administered'' or ``vegetarian fed''; (4) instructional or... Standards and Labeling Policy Book includes animal production claims; omega fatty acid guidance; allergen... inclusion of Country of Origin Labeling on all labels; the production and sale of labels by USDA; developing...

  6. Transgene expression of Drosophila melanogaster nucleoside kinase reverses mitochondrial thymidine kinase 2 deficiency.

    Science.gov (United States)

    Krishnan, Shuba; Zhou, Xiaoshan; Paredes, João A; Kuiper, Raoul V; Curbo, Sophie; Karlsson, Anna

    2013-02-15

    A strategy to reverse the symptoms of thymidine kinase 2 (TK2) deficiency in a mouse model was investigated. The nucleoside kinase from Drosophila melanogaster (Dm-dNK) was expressed in TK2-deficient mice that have been shown to present with a severe phenotype caused by mitochondrial DNA depletion. The Dm-dNK(+/-) transgenic mice were shown to be able to rescue the TK2-deficient mice. The Dm-dNK(+/-)TK2(-/-) mice were normal as judged by growth and behavior during the observation time of 6 months. The Dm-dNK-expressing mice showed a substantial increase in thymidine-phosphorylating activity in investigated tissues. The Dm-dNK expression also resulted in highly elevated dTTP pools. The dTTP pool alterations did not cause specific mitochondrial DNA mutations or deletions when 6-month-old mice were analyzed. The mitochondrial DNA was also detected at normal levels. In conclusion, the Dm-dNK(+/-)TK2(-/-) mouse model illustrates how dTMP synthesized in the cell nucleus can compensate for loss of intramitochondrial dTMP synthesis in differentiated tissue. The data presented open new possibilities to treat the severe symptoms of TK2 deficiency.

  7. Transgene Expression of Drosophila melanogaster Nucleoside Kinase Reverses Mitochondrial Thymidine Kinase 2 Deficiency*♦

    Science.gov (United States)

    Krishnan, Shuba; Zhou, Xiaoshan; Paredes, João A.; Kuiper, Raoul V.; Curbo, Sophie; Karlsson, Anna

    2013-01-01

    A strategy to reverse the symptoms of thymidine kinase 2 (TK2) deficiency in a mouse model was investigated. The nucleoside kinase from Drosophila melanogaster (Dm-dNK) was expressed in TK2-deficient mice that have been shown to present with a severe phenotype caused by mitochondrial DNA depletion. The Dm-dNK+/− transgenic mice were shown to be able to rescue the TK2-deficient mice. The Dm-dNK+/−TK2−/− mice were normal as judged by growth and behavior during the observation time of 6 months. The Dm-dNK-expressing mice showed a substantial increase in thymidine-phosphorylating activity in investigated tissues. The Dm-dNK expression also resulted in highly elevated dTTP pools. The dTTP pool alterations did not cause specific mitochondrial DNA mutations or deletions when 6-month-old mice were analyzed. The mitochondrial DNA was also detected at normal levels. In conclusion, the Dm-dNK+/−TK2−/− mouse model illustrates how dTMP synthesized in the cell nucleus can compensate for loss of intramitochondrial dTMP synthesis in differentiated tissue. The data presented open new possibilities to treat the severe symptoms of TK2 deficiency. PMID:23288848

  8. The Dipeptide Monoester Prodrugs of Floxuridine and Gemcitabine—Feasibility of Orally Administrable Nucleoside Analogs

    Directory of Open Access Journals (Sweden)

    Yasuhiro Tsume

    2014-01-01

    Full Text Available Dipeptide monoester prodrugs of floxuridine and gemcitabine were synthesized. Their chemical stability in buffers, enzymatic stability in cell homogenates, permeability in mouse intestinal membrane along with drug concentration in mouse plasma, and anti-proliferative activity in cancer cells were determined and compared to their parent drugs. Floxuridine prodrug was more enzymatically stable than floxuridine and the degradation from prodrug to parent drug works as the rate-limiting step. On the other hand, gemcitabine prodrug was less enzymatically stable than gemcitabine. Those dipeptide monoester prodrugs exhibited 2.4- to 48.7-fold higher uptake than their parent drugs in Caco-2, Panc-1, and AsPC-1 cells. Floxuridine and gemcitabine prodrugs showed superior permeability in mouse jejunum to their parent drugs and exhibited the higher drug concentration in plasma after in situ mouse perfusion. Cell proliferation assays in ductal pancreatic cancer cells, AsPC-1 and Panc-1, indicated that dipeptide prodrugs of floxuridine and gemcitabine were more potent than their parent drugs. The enhanced potency of nucleoside analogs was attributed to their improved membrane permeability. The prodrug forms of 5¢-L-phenylalanyl-l-tyrosyl-floxuridine and 5¢-L-phenylalanyl-L-tyrosyl-gemcitabine appeared in mouse plasma after the permeation of intestinal membrane and the first-pass effect, suggesting their potential for the development of oral dosage form for anti-cancer agents.

  9. Enzymatic primer-extension with glycerol-nucleoside triphosphates on DNA templates.

    Directory of Open Access Journals (Sweden)

    Jesse J Chen

    Full Text Available BACKGROUND: Glycerol nucleic acid (GNA has an acyclic phosphoglycerol backbone repeat-unit, but forms stable duplexes based on Watson-Crick base-pairing. Because of its structural simplicity, GNA is of particular interest with respect to the possibility of evolving functional polymers by in vitro selection. Template-dependent GNA synthesis is essential to any GNA-based selection system. PRINCIPAL FINDINGS: In this study, we investigated the ability of various DNA polymerases to use glycerol-nucleoside triphosphates (gNTPs as substrates for GNA synthesis on DNA templates. Therminator DNA polymerase catalyzes quantitative primer-extension by the incorporation of two glyceronucleotides, with much less efficient extension up to five glyceronucleotides. Steady-state kinetic experiments suggested that GNA synthesis by Therminator was affected by both decreased catalytic rates and weakened substrate binding, especially for pyrimidines. In an attempt to improve pyrimidine incorporation by providing additional stacking interactions, we synthesized two new gNTP analogs with 5-propynyl substituted pyrimidine nucleobases. This led to more efficient incorporation of gC, but not gT. CONCLUSIONS: We suggest that directed evolution of Therminator might lead to mutants with improved substrate binding and catalytic efficiency.

  10. Tunnel conductance of Watson-Crick nucleoside-base pairs from telegraph noise

    International Nuclear Information System (INIS)

    Chang Shuai; He Jin; Lin Lisha; Zhang Peiming; Liang Feng; Huang Shuo; Lindsay, Stuart; Young, Michael

    2009-01-01

    The use of tunneling signals to sequence DNA is presently hampered by the small tunnel conductance of a junction spanning an entire DNA molecule. The design of a readout system that uses a shorter tunneling path requires knowledge of the absolute conductance across base pairs. We have exploited the stochastic switching of hydrogen-bonded DNA base-nucleoside pairs trapped in a tunnel junction to determine the conductance of individual molecular pairs. This conductance is found to be sensitive to the geometry of the junction, but a subset of the data appears to come from unstrained molecular pairs. The conductances determined from these pairs are within a factor of two of the predictions of density functional calculations. The experimental data reproduces the counterintuitive theoretical prediction that guanine-deoxycytidine pairs (3 H-bonds) have a smaller conductance than adenine-thymine pairs (2 H-bonds). A bimodal distribution of switching lifetimes shows that both H-bonds and molecule-metal contacts break.

  11. TNF α is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

    Science.gov (United States)

    Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin

    2011-01-01

    In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTI). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2′,3′-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain. PMID:21741472

  12. Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA vaccine of Leishmania donovani.

    Science.gov (United States)

    Gamboa-León, R; Paraguai de Souza, E; Borja-Cabrera, G P; Santos, F N; Myashiro, L M; Pinheiro, R O; Dumonteil, E; Palatnik-de-Sousa, C B

    2006-05-29

    The nucleoside hydrolase (NH36) of Leishmania (L.) donovani is a vital enzyme which releases purines or pyrimidines of foreign DNA to be used in the synthesis of parasite DNA. As a bivalent DNA vaccine, the VR1012-NH36 was immunoprotective against visceral and cutaneous murine leishmaniasis. In this work we tested the immunotherapy against Leishmania (L.) chagasi infection, using two doses of 100 or 20 microg VR1012-NH36 vaccine (i.m. route), and, as a possible immunomodulator, aqueous garlic extract (8 mg/kg/day by the i.p. route), which was effective in immunotherapy of cutaneous murine leishmaniasis. Liver parasitic load was significantly reduced following treatment with 100 microg (91%) and 20 microg (77%) of the DNA vaccine, and by 20 microg DNA vaccine and garlic extract (76%) (p=0.023). Survival was 33% for saline controls, 100% for the 100 microg vaccine, and 83 and 67% for the 20 microg vaccine with and without garlic extract addition, respectively. Garlic treatment alone did not reduce parasite load (p>0.05), but increased survival (100%). The NH36-DNA vaccine was highly effective as a new tool for the therapy and control of visceral leishmaniasis, while the mild protective effect of garlic might be related to an unspecific enhancement of IFN-gamma secretion.

  13. The binding of the primary water of hydration to nucleosides, CsDNA and potassium hyaluronate

    Science.gov (United States)

    Lukan, A. M.; Cavanaugh, D.; Whitson, K. B.; Marlowe, R. L.; Lee, S. A.; Anthony, L.; Rupprecht, A.; Mohan, V.

    1998-03-01

    Differential scanning calorimetry (DSC) has been used to study the eight nucleosides, CsDNA and KHA hydrated at 59% relative humidity. Thermograms were measured between 25 and 180 ^oC for scan rates of 1, 2, 5, 10 and 20 K/min. A broad endothermic transition (due to the desorption of the water) near 80 ^oC was observed for all runs. The average enthalpy of desorption per water molecule was evaluated from the area under the peak. A Kissinger analysis of these data yielded the net activation energy for desorption. Both parameters were very similar for the two biopolymers. Rayleigh scattering of Mossbauer radiation (RSMR) data(G. Albanese et al. ) Hyperfine Int. 95, 97 (1995) were analyzed via a simple harmonic oscillator model to evaluate the effective force constant of the water bound to the biopolymer. This analysis suggests that the effective force constant of water bound to HA is much larger (about 5 times) than for water bound to DNA.

  14. Effect of Purine Nucleoside Analogue-Acyclovir on The Sperm Parameters and Testosterone Production in Rats

    Directory of Open Access Journals (Sweden)

    Vahid Nejati

    2013-01-01

    Full Text Available Background: Acyclovir (ACV, a synthetic purine nucleoside analogue derived fromguanosine, is known to be toxic to gonads and the aim of this study was to evaluate theeffect of ACV on the sperm parameters and testosterone production in rat.Materials and Methods: In this experimental study, forty adult male Wistar rats (220± 20 g were randomly divided into five groups (n=8 for each group. One groupserved as control and one group served as sham control [distilled water was intraperitoneally(i.p. injected]. ACV was administered intraperitoneally in the drugtreatment groups (4, 16 and 48 mg/kg/day for 15 days. Eighteen days after the lastinjection, rats were sacrificed by CO2 inhalation. After that, cauda epididymideswere removed surgically. At the end, sperm concentrations in the cauda epididymis,sperm motility, morphology, viability, chromatin quality and DNA integrity wereanalyzed. Serum testosterone concentrations were determined.Results: The results showed that ACV did not affect sperm count, but decreased spermmotility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increasedat 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damageat 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, asignificant decrease in serum testosterone concentrations was observed at 16 and 48 mg/kg doses.Conclusion: The present results highly support the idea that ACV induces testicular toxicityby adverse effects on the sperm parameters and serum level of testosterone in malerats.

  15. A structural study of lamellar phases formed by nucleoside-functionalized lipids

    Energy Technology Data Exchange (ETDEWEB)

    Berti, D.; Fratini, E.; Baglioni, P. [Department of Chemistry and CSGI, University of Florence, Via G. Capponi 9, 50121 Florence (Italy); Dante, S.; Hauss, T. [Berlin Neutron Scattering Center, Hahn Meitner Institut, Glienicker Strasse 100, Wannsee, 14109 Berlin (Germany)

    2002-07-01

    We report a neutron-scattering investigation of lamellar phases formed by novel phospholipids bearing nucleosides at the polar-head-group region. These nucleolipids can interact through stacking and H-bond interactions, following a pattern that resembles base-base coupling in natural nucleic acids (DNA, RNA), i.e. they have similar recognition properties. Bilayer stacks formed of DPP-adenosine, DPP-uridine and their 1:1 mixture were investigated after equilibration in a 98% relative humidity atmosphere. The DPP-adenosine spectrum can be accounted for (in analogy to DPPC) by a lamellar phase with a smectic period of about 60 A. DPP-uridine displays a not so straightforward behavior that we have tentatively ascribed to the coexistence of lamellae with different smectic periods. In the 1:1 mixture the lamellar mesophase of DPP-uridine is retained, suggesting a specific interaction of the uridine polar-head group with the adenosine moiety of DPP-adenosine. It should be stressed that this behavior can be considered as an indication of the recognition process occurring at the polar-head-group region of the mixed phospholiponucleoside membrane. (orig.)

  16. The therapeutic efficiency of nucleotides and nucleosides in UV radiation edema of mice

    International Nuclear Information System (INIS)

    Kutta, I.

    1973-01-01

    The influence of several nucleotides and nucleosides on UV radiation edemas of mice was studied with the aid of a staining test. In the first test series, amounts equimolar to 20 mg thymidine were injected i.p. It was found that thymidine, ATP, ADP and A5'MP had a significant influence which uridine did not have. The NAD dose of 54.8 mg was lethal in all 10 animals and the ATP dose of 42 mg in three out of 10 animals, while ADP and A5'MP had the effect of a reversible retardation of movements. The most effective substances of this series were ATP and ADP. In the second test series, the substances were equimolar to 1.8 mg thymidine. All substances tested, i.e. thymidine, adenosin, adenosin-cyclophosphate, NAD, NADH, ATP, ADP and A5'MP had a significant effect. Except for NAD, to which the animals reacted with a slight retardation, all substances were well tolerated. NAD and ADP were the most effective. In a third test series, dose-efficiency curves were established for thymidine and ATP. ATP was significantly more effective in equimolar doses. This finding is discussed. (orig.) [de

  17. Preliminary characterization of (nucleoside-2′-O-)-methyltransferase crystals from Meaban and Yokose flaviviruses

    International Nuclear Information System (INIS)

    Mastrangelo, Eloise; Bollati, Michela; Milani, Mario; Lamballeire, Xavier de; Brisbare, Nadege; Dalle, Karen; Lantez, Violaine; Egloff, Marie-Pierre; Coutard, Bruno; Canard, Bruno; Gould, Ernest; Forrester, Naomi; Bolognesi, Martino

    2006-01-01

    Two methyltransferases from flaviviruses (Meaban and Yokose viruses) have been overexpressed and crystallized. Diffraction data and characterization of the two crystal forms are presented, together with a preliminary molecular-replacement solution for both enzymes. Viral methyltranferases (MTase) are involved in the third step of the mRNA-capping process, transferring a methyl group from S-adenosyl-l-methionine (SAM) to the capped mRNA. MTases are classified into two groups: (guanine-N7)-methyltransferases (N7MTases), which add a methyl group onto the N7 atom of guanine, and (nucleoside-2′-O-)-methyltransferases (2′OMTases), which add a methyl group to a ribose hydroxyl. The MTases of two flaviviruses, Meaban and Yokose viruses, have been overexpressed, purified and crystallized in complex with SAM. Characterization of the crystals together with details of preliminary X-ray diffraction data collection (at 2.8 and 2.7 Å resolution, respectively) are reported here. The sequence homology relative to Dengue virus 2′OMTase and the structural conservation of specific residues in the putative active sites suggest that both enzymes belong to the 2′OMTase subgroup

  18. 3D QSAR Studies of DAMNI Analogs as Possible Non-nucleoside Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    S. Ganguly

    2008-01-01

    Full Text Available The non-nucleoside inhibitors of HIV-1-reverse transcriptase (NNRTIs are an important class of drugs employed in antiviral therapy. Recently, a novel family of NNRTIs commonly referred to as 1-[2-diarylmethoxy] ethyl 2-methyl-5-nitroimidazoles (DAMNI derivatives have been discovered. The 3D-QSAR studies on DAMNI derivatives as NNRTIs was performed by comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA methods to determine the factors required for the activity of these compounds. The global minimum energy conformer of the template molecule 15, the most active molecule of the series, was obtained by simulated annealing method and used to build the structures of the molecules in the dataset. The combination of steric and electrostatic fields in CoMSIA gave the best results with cross-validated and conventional correlation coefficients of 0.654 and 0.928 respectively. The predictive ability of CoMFA and CoMSIA were determined using a test set of ten DAMNI derivatives giving predictive correlation coefficients of 0.92 and 0.98 respectively indicating good predictive power. Further, the robustness of the models was verified by bootstrapping analysis. The information obtained from CoMFA and CoMSIA 3D contour maps may be of utility in the design of more potent DAMNI analogs as NNRTIs in future.

  19. 6-methylmercaptopurine riboside, a thiopurine nucleoside with antiviral activity against canine distemper virus in vitro.

    Science.gov (United States)

    de Carvalho, Otávio Valério; Félix, Daniele Mendes; de Camargo Tozato, Claudia; Fietto, Juliana Lopes Rangel; de Almeida, Márcia Rogéria; Bressan, Gustavo Costa; Pena, Lindomar José; Silva-Júnior, Abelardo

    2017-06-26

    Canine distemper (CD) is a widespread infectious disease that can severely impact a variety of species in the order Carnivora, as well as non-carnivore species such as non-human primates. Despite large-scale vaccination campaigns, several fatal outbreaks have been reported in wild and domestic carnivore populations. This, in association with expansion of the disease host range and the development of vaccine-escape strains, has contributed to an increased demand for therapeutic strategies synergizing with vaccine programs for effectively controlling canine distemper. 6-methylmercaptopurine riboside (6MMPr) is a modified thiopurine nucleoside with known antiviral properties against certain RNA viruses. We tested the inhibitory effects of 6MMPr against a wild-type CDV strain infection in cell culture. We measured infectious particle production and viral RNA levels in treated and untreated CDV-infected cells. Ribavirin (RIB) was used as a positive control. Here, we report for the first time the antiviral effects of 6MMPr against canine distemper virus (CDV) in vitro. 6MMPr was able to reduce viral RNA levels and to inhibit the production of infectious CDV particles. The therapeutic selectivity of 6MMPr was approximately six times higher than that of ribavirin. Our results indicate that 6MMPr has high anti-CDV potential and warrants further testing against other paramyxoviruses, as well as clinical testing of the compound against CDV.

  20. Metabolic Recruitment and Directed Evolution of Nucleoside Triphosphate Uptake in Escherichia coli.

    Science.gov (United States)

    Pezo, Valérie; Hassan, Camille; Louis, Dominique; Sargueil, Bruno; Herdewijn, Piet; Marlière, Philippe

    2018-05-18

    We report the design and elaboration of a selection protocol for importing a canonical substrate of DNA polymerase, thymidine triphosphate (dTTP) in Escherichia coli. Bacterial strains whose growth depend on dTTP uptake, through the action of an algal plastid transporter expressed from a synthetic gene inserted in the chromosome, were constructed and shown to withstand the simultaneous loss of thymidylate synthase and thymidine kinase. Such thyA tdk dual deletant strains provide an experimental model of tight nutritional containment for preventing dissemination of microbial GMOs. Our strains transported the four canonical dNTPs, in the following order of preference: dCTP > dATP ≥ dGTP > dTTP. Prolonged cultivation under limitation of exogenous dTTP led to the enhancement of dNTP transport by adaptive evolution. We investigated the uptake of dCTP analogues with altered sugar or nucleobase moieties, which were found to cause a loss of cell viability and an increase of mutant frequency, respectively. E. coli strains equipped with nucleoside triphosphate transporters should be instrumental for evolving organisms whose DNA genome is morphed chemically by fully substituting its canonical nucleotide components.

  1. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    Science.gov (United States)

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  2. Structure-based methods to predict mutational resistance to diarylpyrimidine non-nucleoside reverse transcriptase inhibitors.

    Science.gov (United States)

    Azeem, Syeda Maryam; Muwonge, Alecia N; Thakkar, Nehaben; Lam, Kristina W; Frey, Kathleen M

    2018-01-01

    Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance. In order to aid drug design efforts, it would be efficient and cost effective to pre-evaluate NNRTI compounds in development using a structure-based computational approach. As proof of concept, we applied a residue scan and molecular dynamics strategy using RT crystal structures to predict mutations that confer resistance to DAPYs rilpivirine, etravirine, and investigational microbicide dapivirine. Our predictive values, changes in affinity and stability, are correlative with fold-resistance data for several RT mutants. Consistent with previous studies, mutation K101P is predicted to confer high-level resistance to DAPYs. These findings were further validated using structural analysis, molecular dynamics, and an enzymatic reverse transcription assay. Our results confirm that changes in affinity and stability for mutant complexes are predictive parameters of resistance as validated by experimental and clinical data. In future work, we believe that this computational approach may be useful to predict resistance mutations for inhibitors in development. Published by Elsevier Inc.

  3. Investigation of iron-containing complexes of deoxyribonucleic acid nucleosides by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Greguskova, M.; Novotny, J.; Cernohorsky, I.; Cirak, J.

    1975-01-01

    DNA and nucleoside complexes with ferric and ferrous ions were investigated for the concentration of iron ions, ionic strength, temperature, and the nature and spatial configuration of neighbouring atoms of the iron ions in the complexes. Moessbauer spectroscopy was used. The Moessbauer measurements were conducted on lyophilized samples at room temperature (300 K) and on frozen solutions at liquid nitrogen temperature (77 K). Quadrupole splitting was found in all spectra obtained by a Pd(Co) source, with the exception of thymidine, thus indicating that the formation of complexes had not affected the oxidation state of iron ions. A decrease in isomer shift and an increase in quadrupole splitting were found in all spectra obtained by an iron(III) chloride source as well as in all spectra obtained by an iron chloride tetrahydrate source. UV irradiation of the samples prior to the Moessbauer measurements was found to have no effect on the Moessbauer spectra but to result in changes in the oxidation state of iron ions, mainly their valency and the ferrous/ferric ion ratio. The results are shown in a table and in graphs. (L.O.)

  4. Five putative nucleoside triphosphate diphosphohydrolase genes are expressed in Trichomonas vaginalis.

    Science.gov (United States)

    Frasson, Amanda Piccoli; Dos Santos, Odelta; Meirelles, Lúcia Collares; Macedo, Alexandre José; Tasca, Tiana

    2016-01-01

    Trichomonas vaginalis is a protozoan that parasitizes the human urogenital tract causing trichomoniasis, the most common non-viral sexually transmitted disease. The parasite has unique genomic characteristics such as a large genome size and expanded gene families. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) is an enzyme responsible for hydrolyzing nucleoside tri- and diphosphates and has already been biochemically characterized in T. vaginalis. Considering the important role of this enzyme in the production of extracellular adenosine for parasite uptake, we evaluated the gene expression of five putative NTPDases in T. vaginalis. We showed that all five putative TvNTPDase genes (TvNTPDase1-5) were expressed by both fresh clinical and long-term grown isolates. The amino acid alignment predicted the presence of the five crucial apyrase conserved regions, transmembrane domains, signal peptides, phosphorylation and catalytic sites. Moreover, a phylogenetic analysis showed that TvNTPDase sequences make up a clade with NTPDases intracellularly located. Biochemical NTPDase activity (ATP and ADP hydrolysis) is responsive to the serum-restrictive conditions and the gene expression of TvNTPDases was mostly increased, mainly TvNTPDase2 and TvNTPDase4, although there was not a clear pattern of expression among them. In summary, the present report demonstrates the gene expression patterns of predicted NTPDases in T. vaginalis. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Activation of G-proteins by receptor-stimulated nucleoside diphosphate kinase in Dictyostelium.

    Science.gov (United States)

    Bominaar, A A; Molijn, A C; Pestel, M; Veron, M; Van Haastert, P J

    1993-01-01

    Recently, interest in the enzyme nucleoside diphosphate kinase (EC2.7.4.6) has increased as a result of its possible involvement in cell proliferation and development. Since NDP kinase is one of the major sources of GTP in cells, it has been suggested that the effects of an altered NDP kinase activity on cellular processes might be the result of altered transmembrane signal transduction via guanine nucleotide-binding proteins (G-proteins). In the cellular slime mould Dictyostelium discoideum, extracellular cAMP induces an increase of phospholipase C activity via a surface cAMP receptor and G-proteins. In this paper it is demonstrated that part of the cellular NDP kinase is associated with the membrane and stimulated by cell surface cAMP receptors. The GTP produced by the action of NDP kinase is capable of activating G-proteins as monitored by altered G-protein-receptor interaction and the activation of the effector enzyme phospholipase C. Furthermore, specific monoclonal antibodies inhibit the effect of NDP kinase on G-protein activation. These results suggest that receptor-stimulated NDP kinase contributes to the mediation of hormone action by producing GTP for the activation of GTP-binding proteins. Images PMID:8389692

  6. A structural study of lamellar phases formed by nucleoside-functionalized lipids

    CERN Document Server

    Berti, D; Baglioni, P; Dante, S; Hauss, T

    2002-01-01

    We report a neutron-scattering investigation of lamellar phases formed by novel phospholipids bearing nucleosides at the polar-head-group region. These nucleolipids can interact through stacking and H-bond interactions, following a pattern that resembles base-base coupling in natural nucleic acids (DNA, RNA), i.e. they have similar recognition properties. Bilayer stacks formed of DPP-adenosine, DPP-uridine and their 1:1 mixture were investigated after equilibration in a 98% relative humidity atmosphere. The DPP-adenosine spectrum can be accounted for (in analogy to DPPC) by a lamellar phase with a smectic period of about 60 A. DPP-uridine displays a not so straightforward behavior that we have tentatively ascribed to the coexistence of lamellae with different smectic periods. In the 1:1 mixture the lamellar mesophase of DPP-uridine is retained, suggesting a specific interaction of the uridine polar-head group with the adenosine moiety of DPP-adenosine. It should be stressed that this behavior can be considere...

  7. The dipeptide monoester prodrugs of floxuridine and gemcitabine-feasibility of orally administrable nucleoside analogs.

    Science.gov (United States)

    Tsume, Yasuhiro; Borras Bermejo, Blanca; Amidon, Gordon L

    2014-01-27

    Dipeptide monoester prodrugs of floxuridine and gemcitabine were synthesized. Their chemical stability in buffers, enzymatic stability in cell homogenates, permeability in mouse intestinal membrane along with drug concentration in mouse plasma, and anti-proliferative activity in cancer cells were determined and compared to their parent drugs. Floxuridine prodrug was more enzymatically stable than floxuridine and the degradation from prodrug to parent drug works as the rate-limiting step. On the other hand, gemcitabine prodrug was less enzymatically stable than gemcitabine. Those dipeptide monoester prodrugs exhibited 2.4- to 48.7-fold higher uptake than their parent drugs in Caco-2, Panc-1, and AsPC-1 cells. Floxuridine and gemcitabine prodrugs showed superior permeability in mouse jejunum to their parent drugs and exhibited the higher drug concentration in plasma after in situ mouse perfusion. Cell proliferation assays in ductal pancreatic cancer cells, AsPC-1 and Panc-1, indicated that dipeptide prodrugs of floxuridine and gemcitabine were more potent than their parent drugs. The enhanced potency of nucleoside analogs was attributed to their improved membrane permeability. The prodrug forms of 5¢-L-phenylalanyl-l-tyrosyl-floxuridine and 5¢-L-phenylalanyl-L-tyrosyl-gemcitabine appeared in mouse plasma after the permeation of intestinal membrane and the first-pass effect, suggesting their potential for the development of oral dosage form for anti-cancer agents.

  8. The Dipeptide Monoester Prodrugs of Floxuridine and Gemcitabine—Feasibility of Orally Administrable Nucleoside Analogs

    Science.gov (United States)

    Tsume, Yasuhiro; Bermejo, Blanca Borras; Amidon, Gordon L.

    2014-01-01

    Dipeptide monoester prodrugs of floxuridine and gemcitabine were synthesized. Their chemical stability in buffers, enzymatic stability in cell homogenates, permeability in mouse intestinal membrane along with drug concentration in mouse plasma, and anti-proliferative activity in cancer cells were determined and compared to their parent drugs. Floxuridine prodrug was more enzymatically stable than floxuridine and the degradation from prodrug to parent drug works as the rate-limiting step. On the other hand, gemcitabine prodrug was less enzymatically stable than gemcitabine. Those dipeptide monoester prodrugs exhibited 2.4- to 48.7-fold higher uptake than their parent drugs in Caco-2, Panc-1, and AsPC-1 cells. Floxuridine and gemcitabine prodrugs showed superior permeability in mouse jejunum to their parent drugs and exhibited the higher drug concentration in plasma after in situ mouse perfusion. Cell proliferation assays in ductal pancreatic cancer cells, AsPC-1 and Panc-1, indicated that dipeptide prodrugs of floxuridine and gemcitabine were more potent than their parent drugs. The enhanced potency of nucleoside analogs was attributed to their improved membrane permeability. The prodrug forms of 5′-l-phenylalanyl-l-tyrosyl-floxuridine and 5′-l-phenylalanyl-l-tyrosyl-gemcitabine appeared in mouse plasma after the permeation of intestinal membrane and the first-pass effect, suggesting their potential for the development of oral dosage form for anti-cancer agents. PMID:24473270

  9. Radiochromatographic determination of activity of adenosine deaminase and purine nucleoside phosphorylase in blood cells

    International Nuclear Information System (INIS)

    Pechan, I.; Rendekova, V.; Pechanova, E.; Krizko, J.

    1982-01-01

    Expeditious and sensitive methods are described for determining the activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) in human lymphocytes and erythrocytes. ADA and PNP activity is determined on the basis of the reaction of (U- 14 C)adenosine or (8- 14 C)inosine with the lysate of human blood cells. Reaction products are separated using paper chromatography. Following the measurement of the radioactivity of spots of adenosine, inosine and hypoxanthine, a calculation is made of ADA and PNP activity from the results of the said measurements. On a sample of 52 clinically healthy people average ADA and PNP activity in isolated lymphocytes was found to be (51.6+-18.8) and (185.6+-94.7) pcat/10 6 cells and in erythrocytes (9.8+-2.98) and (17.1+-3.19) pcat/mg of proteins, respectively. The advantage of the method is the small amount of sample needed (1 to 2 ml) which allows its application in pediatrics. (Ha)

  10. Preliminary characterization of (nucleoside-2′-O-)-methyltransferase crystals from Meaban and Yokose flaviviruses

    Energy Technology Data Exchange (ETDEWEB)

    Mastrangelo, Eloise; Bollati, Michela; Milani, Mario [Department of Biomolecular Sciences and Biotechnology, CNR-INFM, University of Milano, Via Celoria 26, 20133 Milano (Italy); Lamballeire, Xavier de; Brisbare, Nadege [Unité des Virus Emergents, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille (France); Dalle, Karen; Lantez, Violaine; Egloff, Marie-Pierre; Coutard, Bruno; Canard, Bruno [Laboratoire Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS ESIL, Case 932, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France); Gould, Ernest; Forrester, Naomi [CEH Oxford, Mansfield Road, Oxford OX1 3SR (United Kingdom); Bolognesi, Martino, E-mail: martino.bolognesi@unimi.it [Department of Biomolecular Sciences and Biotechnology, CNR-INFM, University of Milano, Via Celoria 26, 20133 Milano (Italy)

    2006-08-01

    Two methyltransferases from flaviviruses (Meaban and Yokose viruses) have been overexpressed and crystallized. Diffraction data and characterization of the two crystal forms are presented, together with a preliminary molecular-replacement solution for both enzymes. Viral methyltranferases (MTase) are involved in the third step of the mRNA-capping process, transferring a methyl group from S-adenosyl-l-methionine (SAM) to the capped mRNA. MTases are classified into two groups: (guanine-N7)-methyltransferases (N7MTases), which add a methyl group onto the N7 atom of guanine, and (nucleoside-2′-O-)-methyltransferases (2′OMTases), which add a methyl group to a ribose hydroxyl. The MTases of two flaviviruses, Meaban and Yokose viruses, have been overexpressed, purified and crystallized in complex with SAM. Characterization of the crystals together with details of preliminary X-ray diffraction data collection (at 2.8 and 2.7 Å resolution, respectively) are reported here. The sequence homology relative to Dengue virus 2′OMTase and the structural conservation of specific residues in the putative active sites suggest that both enzymes belong to the 2′OMTase subgroup.

  11. Therapeutic efficiency of nucleotides and nucleosides in UV radiation edema of mice

    Energy Technology Data Exchange (ETDEWEB)

    Kutta, I

    1973-01-01

    The influence of several nucleotides and nucleosides on UV radiation edemas of mice was studied with the aid of a staining test. In the first test series, amounts equimolar to 20 mg thymidine were injected i.p. It was found that thymidine, ATP, ADP and A5'MP had a significant influence which uridine did not have. The NAD dose of 54.8 mg was lethal in all 10 animals and the ATP dose of 42 mg in three out of 10 animals, while ADP and A5'MP had the effect of a reversible retardation of movements. The most effective substances of this series were ATP and ADP. In the second test series, the substances were equimolar to 1.8 mg thymidine. All substances tested, i.e. thymidine, adenosin, adenosin-cyclophosphate, NAD, NADH, ATP, ADP and A5'MP had a significant effect. Except for NAD, to which the animals reacted with a slight retardation, all substances were well tolerated. NAD and ADP were the most effective. In a third test series, dose-efficiency curves were established for thymidine and ATP. ATP was significantly more effective in equimolar doses. This finding is discussed.

  12. Synthesis, characterization and use of Ru-Fc intercalation complex as an electrochemical label for the detection of pathogen-DNA

    International Nuclear Information System (INIS)

    Díaz-Serrano, M; Rosado, A; Guadalupe, A R; Santana, D; Vega, E Z

    2013-01-01

    This report describes the synthesis of [Ru(Fe-Phen) 2 dppz](PF 6 ) 2 (Ru-Fe complex) for a label-free approach to detect DNA hybridization. The Ru-Fe complex showed oxidation signals at +608 mV and +1192 mV corresponding to the RuII/III and FeII/III centers, respectively. We used the Ru-Fe complex and the Ferrocene covalently attached to the target to monitor the hybridization event of a 70-mer oligo immobilized in 10.3KD NHS-PS-NHS. The lowest target detectable concentration for the DNA fragment was around 0.4 μM.

  13. European consumers and nutrition labelling

    DEFF Research Database (Denmark)

    Wills, Josephine M.; Grunert, Klaus G.; Celemín, Laura Fernández

    2009-01-01

    Nutrition labelling of food in Europe is not compulsory, unless a nutrition or health claim is made for the product. The European Commission is proposing mandatory nutrition labelling, even front of pack labelling with nutrition information. Yet, how widespread is nutrition labelling in the EU...

  14. Genetic algorithms for map labeling

    NARCIS (Netherlands)

    Dijk, Steven Ferdinand van

    2001-01-01

    Map labeling is the cartographic problem of placing the names of features (for example cities or rivers) on the map. A good labeling has no intersections between labels. Even basic versions of the problem are NP-hard. In addition, realistic map-labeling problems deal with many cartographic

  15. Radioactive labelling of peptidic hormones

    International Nuclear Information System (INIS)

    Fromageot, P.; Pradelles, P.; Morgat, J.L.; Levine, H.

    1976-01-01

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3 H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  16. Radiopharmaceutical labeling research

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    The objective of this research is to develop methods of attaching radionuclides to monoclonal antibodies and antibody fragments for use in tumor imaging and internal radiation therapy. Monoclonal antibodies and their fragments are of interest because they enable the selective targeting of tumors. The labeled antibodies could be employed as carriers to transport radioisotopes to tumors, thus minimizing total-body radiation dose and radiation damage to normal tissue. Because the time required for labeled antibodies to find the tumor antigen and deliver the dose to the tumor is estimated to be about 1-3 days, radionuclides with a l- to 3-day half-life would be optimum for this purpose. Two of the radionuclides produced at LAMPF, 67 Cu and 77 Br, have the suitable half-life and nuclear-decay properties for use in tumor imaging or therapy with radiolabeled antibodies. These radionuclides and the efforts to prepare radiolabeled antibodies with them are described. We have used three different approaches to meet this objective of labeling antibodies: (1) labeling chelating agents with metal radionuclides, then conjugating the labeled chelating agents to antibodies; (2) conjugating activated chelating agents to antibodies, followed by metalation with metal radionuclides; and (3) radiobrominating small molecules that can be conjugated to antibodies

  17. Fluorine-18 labelled compounds

    International Nuclear Information System (INIS)

    Kleijn, J.P. de

    1978-01-01

    The work presented in this thesis deals with the problems involved in the adaption of reactor-produced fluorine-18 to the synthesis of 18 F-labelled organic fluorine compounds. Several 18 F-labelling reagents were prepared and successfully applied. The limitations to the synthetic possibilities of reactor-produced fluoride- 18 become manifest in the last part of the thesis. An application to the synthesis of labelled aliphatic fluoro amino acids has appeared to be unsuccessful as yet, although some other synthetic approaches can be indicated. Seven journal articles (for which see the availability note) are used to compose the four chapters and three appendices. The connecting text gives a survey of known 18 F-compounds and methods for preparing such compounds. (Auth.)

  18. Synthesis of labeled compounds

    International Nuclear Information System (INIS)

    Whaley, T.W.

    1977-01-01

    Intermediate compounds labeled with 13 C included methane, sodium cyanide, methanol, ethanol, and acetonitrile. A new method for synthesizing 15 N-labeled 4-ethylsulfonyl-1-naphthalene-sulfonamide was developed. Studies were conducted on pathways to oleic-1- 13 C acid and a second pathway investigated was based on carbonation of 8-heptadecynylmagnesium bromide with CO 2 to prepare sterolic acid. Biosynthetic preparations included glucose- 13 C from starch isolated from tobacco leaves following photosynthetic incubation with 13 CO 2 and galactose- 13 C from galactosylglycerol- 13 C from kelp. Research on growth of organisms emphasized photosynthetic growth of algae in which all cellular carbon is labeled. Preliminary experiments were performed to optimize the growth of Escherichia coli on sodium acetate- 13 C

  19. Inhibition and Structure of Trichomonas vaginalis Purine Nucleoside Phosphorylase with Picomolar Transition State Analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rinaldo-Matthis,A.; Wing, C.; Ghanem, M.; Deng, H.; Wu, P.; Gupta, A.; Tyler, P.; Evans, G.; Furneaux, R.; et al.

    2007-01-01

    Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition stte mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a K{sub m}/K{sub d} ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a K{sub m}/K{sub d} ratio of 203,300. The tight binding of DADMe-ImmA supports a late S{sub N}1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP-ImmA{center_dot}PO{sub 4} and TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4} ternary complexes differ from previous structures with substrate anologues. The tight binding with DADMe-ImmA is in part due to a 2.7 {angstrom} ionic interaction between a PO{sub 4} oxygen and the N1 cation of the hydroxypyrrolidine and is weaker in the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure at 3.5 {angstrom}. However, the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4}. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope

  20. Environmental Labels and Declarations

    DEFF Research Database (Denmark)

    Frydendal, Jeppe; Hansen, Lisbeth; Bonou, Alexandra

    2018-01-01

    Based on the terminology and structure developed by the International Organization for Standardization, a description is given on the types of ecolabels that build on life cycle assessments. Focus is on type I labels that point out products and services with an overall environmental preferability...... of labelling, the use of ecolabels in marketing, and the way ecolabels help build a market for “greener products”. Type III labels—or Environmental Product Declarations—are also briefly described with indicative examples from the building sector, a declaration for office furniture, and an introduction is given...... to the European Commission’s programme for product—and organisational environmental footprints ....

  1. Semantic Role Labeling

    CERN Document Server

    Palmer, Martha; Xue, Nianwen

    2011-01-01

    This book is aimed at providing an overview of several aspects of semantic role labeling. Chapter 1 begins with linguistic background on the definition of semantic roles and the controversies surrounding them. Chapter 2 describes how the theories have led to structured lexicons such as FrameNet, VerbNet and the PropBank Frame Files that in turn provide the basis for large scale semantic annotation of corpora. This data has facilitated the development of automatic semantic role labeling systems based on supervised machine learning techniques. Chapter 3 presents the general principles of applyin

  2. Radiolysis of aqueous solutions of nucleosides halogenated at the sugar moiety

    Energy Technology Data Exchange (ETDEWEB)

    Hissung, A; Isildar, M; von Sonntag, C [Max-Planck-Institut fuer Kohlenforschung, Muelheim an der Ruhr (Germany, F.R.). Inst. fuer Strahlenforschung; Witzel, H [Biochemisches Institut der Westfaelischen Wilhelms-Universitaet, Muenster, West Germany

    1981-02-01

    The pulse radiolysis of aqueous solutions of nucleosides halogenated at the sugar moiety (2'-bromo-2'-deoxyuridine 4, 3'-deoxy-3'-iodothymidine 5, 5'-deoxy-5'-iodouridine 6) has been studied. G(Hal) were determined by conductometry varying the experimental conditions (pH, saturation with Ar, N/sub 2/O or air, addition of t-butanol). The results indicate that solvated electrons both add to the nucleobases and eliminate halogen ions from the halogenated sugar moiety. In the case of 4(and possibly of 5) the radical anion of the base transfers (k approximately 10/sup 5/s/sup -1/) an electron to the sugar-bound halogen atom thus cleaving the C-Hal bond. In competition with this reaction there is a protonation of the radical anion of the base by protons and by water. For the latter reaction constant of k = 5 x 10/sup 3/ M/sup -1/s/sup -1/ was estimated. Compound 4 has also been investigated by product analysis after 60-Co-..gamma..-irradiation. In aerated solutions erythrose is formed with a G-value of 0.12. Its precursor radical is the 2'-radical generated from 4 by dissociative electron capture which reacts with O/sub 2/ to the corresponding peroxyl radical. Erythrose is formed after a sequence of reactions, one of which involves the scission of the C-1'-C-2'bond. Under this condition G(HBr) as measured by pulse radiolysis is 0.8. Thus erythrose is formed in 15 per cent yield with respect to its precursor radical. This result is of importance in assessing the precursor radical of a similar product observed in irradiated DNA.

  3. The structure of FIV reverse transcriptase and its implications for non-nucleoside inhibitor resistance.

    Directory of Open Access Journals (Sweden)

    Meytal Galilee

    2018-01-01

    Full Text Available Reverse transcriptase (RT is the target for the majority of anti-HIV-1 drugs. As with all anti-AIDS treatments, continued success of RT inhibitors is persistently disrupted by the occurrence of resistance mutations. To explore latent resistance mechanisms potentially accessible to therapeutically challenged HIV-1 viruses, we examined RT from the related feline immunodeficiency virus (FIV. FIV closely parallels HIV-1 in its replication and pathogenicity, however, is resistant to all non-nucleoside inhibitors (NNRTI. The intrinsic resistance of FIV RT is particularly interesting since FIV harbors the Y181 and Y188 sensitivity residues absent in both HIV-2 and SIV. Unlike RT from HIV-2 or SIV, previous efforts have failed to make FIV RT susceptible to NNRTIs concluding that the structure or flexibility of the feline enzyme must be profoundly different. We report the first crystal structure of FIV RT and, being the first structure of an RT from a non-primate lentivirus, enrich the structural and species repertoires available for RT. The structure demonstrates that while the NNRTI binding pocket is conserved, minor subtleties at the entryway can render the FIV RT pocket more restricted and unfavorable for effective NNRTI binding. Measuring NNRTI binding affinity to FIV RT shows that the "closed" pocket configuration inhibits NNRTI binding. Mutating the loop residues rimming the entryway of FIV RT pocket allows for NNRTI binding, however, it does not confer sensitivity to these inhibitors. This reveals a further layer of resistance caused by inherent FIV RT variances that could have enhanced the dissociation of bound inhibitors, or, perhaps, modulated protein plasticity to overcome inhibitory effects of bound NNRTIs. The more "closed" conformation of FIV RT pocket can provide a template for the development of innovative drugs that could unlock the constrained pocket, and the resilient mutant version of the enzyme can offer a fresh model for the study

  4. Radiolysis of aqueous solutions of nucleosides halogenated at the sugar moiety

    International Nuclear Information System (INIS)

    Hissung, A.; Isildar, M.; Sonntag, C. von; Witzel, H.

    1981-01-01

    The pulse radiolysis of aqueous solutions of nucleosides halogenated at the sugar moiety (2'-bromo-2'-deoxyuridine 4, 3'-deoxy-3'-iodothymidine 5, 5'-deoxy-5'-iodouridine 6) has been studied. G(Hal) were determined by conductometry varying the experimental conditions (pH, saturation with Ar, N 2 O or air, addition of t-butanol). The results indicate that solvated electrons both add to the nucleobases and eliminate halogen ions from the halogenated sugar moiety. In the case of 4(and possibly of 5) the radical anion of the base transfers (k approximately 10 5 s -1 ) an electron to the sugar-bound halogen atom thus cleaving the C-Hal bond. In competition with this reaction there is a protonation of the radical anion of the base by protons and by water. For the latter reaction constant of k = 5 x 10 3 M -1 s -1 was estimated. Compound 4 has also been investigated by product analysis after 60-Co-γ-irradiation. In aerated solutions erythrose is formed with a G-value of 0.12. Its precursor radical is the 2'-radical generated from 4 by dissociative electron capture which reacts with O 2 to the corresponding peroxyl radical. Erythrose is formed after a sequence of reactions, one of which involves the scission of the C-1'-C-2'bond. Under this condition G(HBr) as measured by pulse radiolysis is 0.8. Thus erythrose is formed in 15 per cent yield with respect to its precursor radical. This result is of importance in assessing the precursor radical of a similar product observed in irradiated DNA. (author)

  5. Comparison of agrobacterium mediated wheat and barley transformation with nucleoside diphosphate kinase 2 (NDPK2) gene

    International Nuclear Information System (INIS)

    Waheed, U.; Shah, M.M.; Smedley, M.; Harwood, W.

    2016-01-01

    An efficient and reliable transformation system is imperative for improvement of important crop species like barley and wheat. Wheat transformation is complex due to larger genome size and polyploidy while barley has a limitation of genotypic dependency. The objective of current study was to compare the relative transformation efficiency of wheat and barley using specific expression vector pBRACT 214-NDPK2 constructed through gateway cloning carrying Nucleoside Diphosphate Kinase 2 (NDPK2) gene. The vector was used to compare the transformation response in both crops using immature embryos through Agrobacterium mediated transformation. Both wheat and barley showed different responses towards callus induction and regeneration. Immature embryos of 1.5 to 2 mm in diameter was found optimum for wheat callus induction while 1 to 1.5 mm for barley. Both embryogenic and non-embryogenic calli were found in wheat with significantly greater tendency for embryogenecity in barley. The overall regeneration response was found different for all transformed wheat and barley cultivars. Wheat cultivars showed good response initially that drastically slowed down in later stages with the exception of Fielder that reached to the green shoots with good roots. The barley transformed lines showed good regeneration response as compared to wheat. PCR analysis of putative transformants using genomic DNA showed a maximum of 27% transformation efficiency in barely. No true transformation response was obtained in all cultivars of wheat used in this study. The protocol developed for wheat and barley transformation will greatly be helpful in crop improvement programme through genetic engineering especially in diploid relatives of cereals. (author)

  6. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

  7. Identification of a dithiol-dependent nucleoside triphosphate hydrolase in Sarcocystis neurona.

    Science.gov (United States)

    Zhang, Deqing; Gaji, Rajshekhar Y; Howe, Daniel K

    2006-09-01

    A putative nucleoside triphosphate hydrolase (NTPase) gene was identified in a database of expressed sequence tags (ESTs) from the apicomplexan parasite Sarcocystis neurona. Analysis of culture-derived S. neurona merozoites demonstrated a dithiol-dependent NTPase activity, consistent with the presence of a homologue to the TgNTPases of Toxoplasma gondii. A complete cDNA was obtained for the S. neurona gene and the predicted amino acid sequence shared 38% identity with the two TgNTPase isoforms from T. gondii. Based on the obvious homology, the S. neurona protein was designated SnNTP1. The SnNTP1 cDNA encodes a polypeptide of 714 amino acids with a predicted 22-residue signal peptide and an estimated mature molecular mass of 70kDa. Southern blot analysis of the SnNTP1 locus revealed that the gene exists as a single copy in the S. neurona genome, unlike the multiple gene copies that have been observed in T. gondii and Neospora caninum. Analyses of the SnNTP1 protein demonstrated that it is soluble and secreted into the culture medium by extracellular merozoites. Surprisingly, indirect immunofluorescence analysis of intracellular S. neurona revealed apical localisation of SnNTP1 and temporal expression characteristics that are comparable with the microneme protein SnMIC10. The absence of SnNTP1 during much of endopolygeny implies that this protein does not serve a function during intracellular growth and development of S. neurona schizonts. Instead, SnNTP1 may play a role in events that occur during or proximal to merozoite egress from and/or invasion into cells.

  8. Interactions of radiation with novel chemotherapeutic agents: Taxanes and nucleoside analogs

    International Nuclear Information System (INIS)

    Milas, Luka

    1997-01-01

    The combination of chemotherapeutic agents and radiotherapy is an appealing approach to improving the results of cancer treatment. By their independent action or interactive action chemotherapeutic drugs reduce cell burden in tumors undergoing radiotherapy, thereby increasing the chances of tumor control. In addition, the drugs may spatially cooperate with radiotherapy through their systemic action on metastatic disease. Recently, a number of new chemotherapeutic agents have been introduced for cancer treatment, which in addition have high potential to increase therapeutic ratio of radiotherapy. These agents include taxanes (paclitaxel and docetaxel) and the nucleoside analogs fludarabine and gemcitabine. Paclitaxel is a natural product isolated from the bark of Taxus brevifolia and taxotere is a semisynthetic analogue of paclitaxel prepared from needle extracts of Taxus baccata. By binding to cellular tubulin structures, taxanes interfere with tubulin polymerization and promote microtubule assembly, resulting in accumulation of cells in the radiosensitive G2 and M phases of the cell cycle. In vivo studies have demonstrated two major mechanisms of tumor radioenhancement by taxanes: mitotic arrest and tumor reoxygenation. Fludarabine and gemcitabine inhibit DNA synthesis and the repair of radiation-induced chromosome breaks. The mechanism of their radioenhancing activity include inhibition of repair of radiation induced damage, apoptosis induction and cell cycle synchronization. Because both classes of these agents affect radioresponse of normal dose-limiting tissues much less than that of tumors, they can greatly increase therapeutic ratio of radiotherapy. The objective of this course is to overview the rationale for using these drugs as radioenhancing agents, the experimental findings in preclinical studies, the mechanisms of their interaction, and the clinical application of these agents

  9. Electrochemical impedance spectroscopy for analytical determination of paraquat in meconium samples using an immunosensor modified with fullerene, ferrocene and ionic liquid

    Energy Technology Data Exchange (ETDEWEB)

    Sun Xiulan [State Key Laboratory of Food Science and Technology, Wuxi 214122 (China); Li Zaijun, E-mail: zaijunli@263.ne [School of Chemical and Materials Engineering, Jiangnan University, Lihu Road 1800, Wuxi 214122 (China); Cai, Yan; Wei, Zhilei [School of Chemical and Materials Engineering, Jiangnan University, Lihu Road 1800, Wuxi 214122 (China); Fang Yinjun; Ren Guoxiao; Huang Yaru [Zhejiang Zanyu Technology Limited Corporation, Hangzhou 311215 (China)

    2011-01-01

    The paper reports a highly sensitive electrochemical immunosensor for the detection of paraquat. The immunosensor bases on glassy carbon electrode modified with a composite made from fullerene, ferrocene and the ionic liquid. The components were immobilized on the electrode surface by chitosan. The antibody of paraquat was covalently conjugated to the surface which was then blocked with bovine serum albumin. Analytical characteristics of the immunosensor were investigated by electrochemical impedance spectroscopy. It offers good repeatability (RSD = 1.5%), a stability of more than 150 days, an impedimetric response to paraquat in the range from 3.89 x 10{sup -11} to 4.0 x 10{sup -8} mol L{sup -1}, and a detection limit (S/N = 3) of 9.0 x 10{sup -12} mol L{sup -1}. The effects of omitting fullerene and the ionic liquid were well tested. The results indicated that sensitivity of the immunosensor is 3.7-fold better if fullerene and ionic liquid are used. This demonstrates that fullerene facilitates electron transfer on surface of the electrode due to unique electrochemical properties, while the ionic liquid provides biocompatible microenvironment for the antibody, which results in the enhanced sensitivity and stability. Moreover, surface morphology feature and electrochemical properties of the electrode were also examined. The method was satisfactorily applied to the determination of paraquat in meconium.

  10. Ferrocene-catalyzed heterogeneous Fenton-like degradation mechanisms and pathways of antibiotics under simulated sunlight: A case study of sulfamethoxazole.

    Science.gov (United States)

    Li, Yingjie; Zhang, Biaojun; Liu, Xiangliang; Zhao, Qun; Zhang, Heming; Zhang, Yuechao; Ning, Ping; Tian, Senlin

    2018-07-05

    Readily-available and efficient catalyst is essential for activating oxidants to produce reactive species for deeply remediating water bodies contaminated by antibiotics. In this study, Ferrocene (Fc) was introduced to establish a heterogeneous photo-Fenton system for the degradation of sulfonamide antibiotics, taking sulfamethoxazole as a representative. Results showed that the removal of sulfamethoxazole was effective in Fc-catalyzed photo-Fenton system. Electron spin resonance and radical scavenging experiments verified that there was a photoindued electron transfer process from Fc to H 2 O 2 and dissolved oxygen resulting in the formation of OH that was primarily responsible for the degradation of sulfamethoxazole. The reactions of OH with substructure model compounds of sulfamethoxazole unveiled that aniline moiety was the preferable reaction site of sulfamethoxazole, which was verified by the formation of hydroxylated product and the dimer of sulfamethoxazole in Fc-catalyzed photo-Fenton system. This heterogeneous photo-Fenton system displayed an effective degradation efficiency even in a complex water matrices, and Fc represented a long-term stability by using the catalyst for multiple cycles. These results demonstrate that Fc-catalyzed photo-Fenton oxidation may be an efficient approach for remediation of wastewater containing antibiotics. Copyright © 2018. Published by Elsevier B.V.

  11. Metabolic signature of breast cancer cell line MCF-7: profiling of modified nucleosides via LC-IT MS coupling

    Directory of Open Access Journals (Sweden)

    Gleiter Christoph H

    2007-11-01

    Full Text Available Abstract Background Cancer, like other diseases accompanied by strong metabolic disorders, shows characteristic effects on cell turnover rate, activity of modifying enzymes and DNA/RNA modifications, resulting also in elevated amounts of excreted modified nucleosides. For a better understanding of the impaired RNA metabolism in breast cancer cells, we screened these metabolites in the cell culture supernatants of the breast cancer cell line MCF-7 and compared it to the human mammary epithelial cells MCF-10A. The nucleosides were isolated and analyzed via 2D-chromatographic techniques: In the first dimension by cis-diol specific boronate affinity extraction and subsequently by reversed phase chromatography coupled to an ion trap mass spectrometer. Results Besides the determination of ribonucleosides, additional compounds with cis-diol structure, deriving from cross-linked biochemical pathways, like purine-, histidine- and polyamine metabolism were detected. In total, 36 metabolites were identified by comparison of fragmentation patterns and retention time. Relation to the internal standard isoguanosine yielded normalized area ratios for each identified compound and enabled a semi-quantitative metabolic signature of both analyzed cell lines. 13 of the identified 26 modified ribonucleosides were elevated in the cell culture supernatants of MCF-7 cells, with 5-methyluridine, N2,N2,7-trimethylguanosine, N6-methyl-N6-threonylcarbamoyladenosine and 3-(3-aminocarboxypropyl-uridine showing the most significant differences. 1-ribosylimidazole-4-acetic acid, a histamine metabolite, was solely found in the supernatants of MCF-10A cells, whereas 1-ribosyl-4-carboxamido-5-aminoimidazole and S-adenosylmethionine occurred only in supernatants of MCF-7 cells. Conclusion The obtained results are discussed against the background of pathological changes in cell metabolism, resulting in new perspectives for modified nucleosides and related metabolites as possible

  12. Simultaneous determination of nucleosides, myriocin, and carbohydrates in Cordyceps by HPLC coupled with diode array detection and evaporative light scattering detection.

    Science.gov (United States)

    Wang, Shuang; Yang, Feng-Qing; Feng, Kun; Li, De-Qiang; Zhao, Jing; Li, Shao-Ping

    2009-12-01

    A HPLC coupled with diode array detection (DAD) and evaporative light scattering detection (ELSD) method for qualitative and quantitative analysis of eight nucleosides and nucleobases, three carbohydrates and myriocin in Cordyceps was developed. A Prevail Carbohydrate ES column was employed for the separation within 50 min. Nucleosides and their bases were tested at UV 254 nm. ELSD was connected with DAD to determine myriocin and carbohydrates. The optimum drift tube temperature of ELSD was at 94 degrees C with the nitrogen flow rate of 2.0 L/min. All calibration curves showed good linearity (R(2)>0.9933) during the test ranges. The precision, repeatability, accuracy, LOD and LOQ were also fully investigated. This developed method was successfully applied to quantify 12 components, eight nucleosides and nucleobases, three carbohydrates and myriocin, in natural and cultured Cordyceps, which provides another view for quality control of Cordyceps sinensis.

  13. Pyrrolo[2,3-d]pyrimidine (7-deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

    Czech Academy of Sciences Publication Activity Database

    Perlíková, Pavla; Hocek, Michal

    2017-01-01

    Roč. 37, č. 6 (2017), s. 1429-1460 ISSN 0198-6325 R&D Projects: GA ČR(CZ) GA16-00178S Grant - others:AV ČR(CZ) AP1501 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:61388963 Keywords : antivirals * cytostatics * deazapurines * nucleosides * nucleotides Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 8.763, year: 2016 http://onlinelibrary.wiley.com/doi/10.1002/med.21465/full

  14. Synthesis of substituted mono- and diindole C-nucleoside analogues from sugar terminal alkynes by sequential sonogashira/heteroannulation reaction.

    Science.gov (United States)

    Zhang, Fuyi; Mu, Delong; Wang, Liming; Du, Pengfei; Han, Fen; Zhao, Yufen

    2014-10-17

    The synthesis of substituted mono- and diindole C-nucleoside analogues has been achieved in good to excellent yields by sequential Sonogashira coupling/NaAuCl4-catalyzed heteroannulation reactions of substituted 2-iodoanilines with various sugar terminal alkynes in one pot. The method is general, mild, and efficient and suitable for a wide range of sugar substrates, and 42 examples are given. The amino group of the substituted 2-iodoanilines is unprotected. The sugar terminal alkynes include furanosides, pyranosides, and acyclic glycosides with free hydroxyl groups, sensitive functional subtituents, and various protecting groups having different steric hindrance.

  15. Competing Environmental Labels

    NARCIS (Netherlands)

    Fischer, Carolyn; Lyon, Thomas P.

    2014-01-01

    We study markets in which consumers prefer green products but cannot determine the environmental quality of any given firm's product on their own. A nongovernmental organization (NGO) can establish a voluntary standard and label products that comply with it. Alternatively, industry can create its

  16. The Language of Labels

    Science.gov (United States)

    Markham, Darcy

    2005-01-01

    The author describes how the language of labels and her own cultural biases affect how she approaches teaching her students with disabilities. The author examines how the mythopoetic narratives of our past force us to examine the underlying assumptions of our culture that are expressed within our language and how understanding our own linguistic…

  17. Labeling of Cosmetic Products

    Directory of Open Access Journals (Sweden)

    Nicola Lionetti

    2018-03-01

    Full Text Available The labeling of cosmetic products provides a set of obligations, as reported in the Regulation 1223/2009, which came into force in Europe in July 2013. The indications reported on the label are intended to enable the clear identification of the functionality and proper use of cosmetics, ensure the protection of the consumer from the commercial aspects and, above all, from the safety point of view. Moreover, it should allow quick tracing of the product details and all info of toxicological relevance. However, the misuse of this tool often leads, on one side, to confusion among cosmetics, pharmaceuticals, medical devices, and biocides. On the other side, it gives rise to fanciful interpretations by a huge number of web users, who pretend to be able to judge the quality of a cosmetic product just by reading the ingredients list. This article points out the concrete purpose of cosmetic labels, in order to shed light on the use of certain categories of ‘controversial’ ingredients and on the real quality concepts of cosmetic products. Indeed, when properly interpreted, cosmetic labels represent a good tool for the professional investigation of adverse reactions to cosmetics.

  18. Label Review Training: Module 1: Label Basics, Page 7

    Science.gov (United States)

    Page 7, Label Training, Pesticide labels translate results of our extensive evaluations of pesticide products into conditions, directions and precautions that define parameters for use of a pesticide with the goal of ensuring protection of human he

  19. New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, X-ray crystallography and anticancer activity.

    Science.gov (United States)

    Tănase, Constantin I; Drăghici, Constantin; Căproiu, Miron Teodor; Shova, Sergiu; Mathe, Christophe; Cocu, Florea G; Enache, Cristian; Maganu, Maria

    2014-01-01

    An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane skeleton in the sugar moiety. X-ray crystallography confirmed an exo-coupling of base to the ring and a L configuration of the nucleoside analogues. The compounds were tested for anticancer activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. A new application of scanning electrochemical microscopy for the label-free interrogation of antibody-antigen interactions

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, Joanne L.; Davis, Frank; Collyer, Stuart D. [Cranfield Health, Cranfield University, Cranfield, MK43 0AL (United Kingdom); Higson, Seamus P.J., E-mail: s.p.j.higson@cranfield.ac.uk [Cranfield Health, Cranfield University, Cranfield, MK43 0AL (United Kingdom)

    2011-03-18

    Within this work we present a 'proof of principle' study for the use of scanning electrochemical microscopy (SECM) to detect and image biomolecular interactions in a label-free assay as a potential alternative to current fluorescence techniques. Screen-printed carbon electrodes were used as the substrate for the deposition of a dotted array, where the dots consist of biotinylated polyethyleneimine. These were then further derivatised, first with neutravidin and then with a biotinylated antibody to the protein neuron specific enolase (NSE). SECM using a ferrocene carboxylic acid mediator showed clear differences between the array and the surrounding unmodified carbon. Imaging of the arrays before and following exposure to various concentrations of the antigen showed clear evidence for specific binding of the NSE antigen to the antibody derivatised dots. Non-specific binding was quantified. Control experiments with other proteins showed only non-specific binding across the whole of the substrate, thereby confirming that specific binding does occur between the antibody and antigen at the surface of the dots. Binding of the antigen was accompanied by a measured increase in current response, which may be explained in terms of protein electrostatic interaction and hydrophobic interactions to the mediator, thereby increasing the localised mediator flux. A calibration curve was obtained between 500 fg mL{sup -1} to 200 pg mL{sup -1} NSE which demonstrated a logarithmic relationship between the current change upon binding and antigen concentration without the need for any labelling of the substrate.

  1. Spin labels. Applications in biology

    International Nuclear Information System (INIS)

    Frangopol, T.P.; Frangopol, M.; Ionescu, S.M.; Pop, I.V.; Benga, G.

    1980-11-01

    The main applications of spin labels in the study of biomembranes, enzymes, nucleic acids, in pharmacology, spin immunoassay are reviewed along with the fundamentals of the spin label method. 137 references. (author)

  2. Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications

    Directory of Open Access Journals (Sweden)

    Kiss David S

    2009-04-01

    Full Text Available Abstract Background Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3 may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR hypothalamic structures in the rat brain, here we investigated: 1. The cellular and subcellular localization of NTPDase3; 2. The effects of 17β-estradiol on the expression level of hypothalamic NTPDase3; and 3. The effects of NTPDase inhibition in hypothalamic synaptosomal preparations. Methods Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode. Results Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD indicated that γ-amino-butyric-acid- (GABA ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of

  3. Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Yeonju Lee

    Full Text Available We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1, a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated N-cadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT. Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.

  4. Fast Simultaneous Determination of 13 Nucleosides and Nucleobases in Cordyceps sinensis by UHPLC–ESI–MS/MS

    Directory of Open Access Journals (Sweden)

    Shi-Yu Zong

    2015-12-01

    Full Text Available A reliable ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS method for the fast simultaneous determination of 13 nucleosides and nucleobases in Cordyceps sinensis (C. sinensis with 2-chloroadenosine as internal standard was developed and validated. Samples were ultrasonically extracted in an ice bath thrice, and the optimum analyte separation was performed on an ACQUITY UPLCTM HSS C18 column (100 mm × 2.1 mm, 1.8 μm with gradient elution. All targeted analytes were separated in 5.5 min. Furthermore, all calibration curves showed good linear regression (r > 0.9970 within the test ranges, and the limits of quantitation and detection of the 13 analytes were less than 150 and 75 ng/mL, respectively. The relative standard deviations (RSDs of intra- and inter-day precisions were <6.23%. Recoveries of the quantified analytes ranged within 85.3%–117.3%, with RSD < 6.18%. The developed UHPLC–ESI–MS/MS method was successfully applied to determine nucleosides and nucleobases in 11 batches of C. sinensis samples from different regions in China. The range for the total content in the analyzed samples was 1329–2057 µg/g.

  5. Ergopeptines bromocriptine and ergovaline and the dopamine type-2 receptor inhibitor domperidone inhibit bovine equilibrative nucleoside transporter 1-like activity.

    Science.gov (United States)

    Miles, Edwena D; Xue, Yan; Strickland, James R; Boling, James A; Matthews, James C

    2011-09-14

    Neotyphodium coenophialum-infected tall fescue contains ergopeptines. Except for interactions with biogenic amine receptors (e.g., dopamine type-2 receptor, D2R), little is known about how ergopeptines affect animal metabolism. The effect of ergopeptines on bovine nucleoside transporters (NT) was evaluated using Madin-Darby bovine kidney (MDBK) cells. Equilibrative NT1 (ENT1)-like activity accounted for 94% of total NT activity. Inhibitory competition (IC(50)) experiments found that this activity was inhibited by both bromocriptine (a synthetic model ergopeptine and D2R agonist) and ergovaline (a predominant ergopeptine of tall fescue). Kinetic inhibition analysis indicated that bromocriptine inhibited ENT1-like activity through a competitive and noncompetitive mechanism. Domperidone (a D2R antagonist) inhibited ENT1 activity more in the presence than in the absence of bromocriptine and displayed an IC(50) value lower than that of bromocriptine or ergovaline, suggesting that inhibition was not through D2R-mediated events. These novel mechanistic findings imply that cattle consuming endophyte-infected tall fescue have reduced ENT1 activity and, thus, impaired nucleoside metabolism.

  6. Production, purification, crystallization and preliminary X-ray diffraction studies of the nucleoside diphosphate kinase b from Leishmania major

    International Nuclear Information System (INIS)

    Tonoli, Celisa Caldana Costa; Vieira, Plinio Salmazo; Ward, Richard John; Arni, Raghuvir Krishnaswamy; Oliveira, Arthur Henrique Cavalcante de; Murakami, Mario Tyago

    2009-01-01

    Overexpression, purification, crystallization and preliminary X-ray diffraction analysis of the nucleoside diphosphate kinase b from Leishmania major are reported. The crystals belonged to the trigonal space group P3 2 21 and diffracted to 2.18 Å resolution. Nucleoside diphosphate kinases (NDKs; EC 2.7.4.6) play an essential role in the synthesis of nucleotides from intermediates in the salvage pathway in all parasitic trypanosomatids and their structural studies will be instrumental in shedding light on the biochemical machinery involved in the parasite life cycle and host–parasite interactions. In this work, NDKb from Leishmania major was overexpressed in Escherichia coli, purified to homogeneity and crystallized using the sitting-drop vapour-diffusion method. The NDK crystal diffracted to 2.2 Å resolution and belonged to the trigonal crystal system, with unit-cell parameters a = 114.2, c = 93.9 Å. Translation-function calculations yielded an unambiguous solution in the enantiomorphic space group P3 2 21

  7. Nucleoside uptake in macrophages from various murine strains: a short-time and a two-step stimulation model

    International Nuclear Information System (INIS)

    Busolo, F.; Conventi, L.; Grigolon, M.; Palu, G.

    1991-01-01

    Kinetics of [3H]-uridine uptake by murine peritoneal macrophages (pM phi) is early altered after exposure to a variety of stimuli. Alterations caused by Candida albicans, lipopolysaccharide (LPS) and recombinant interferon-gamma (rIFN-gamma) were similar in SAVO, C57BL/6, C3H/HeN and C3H/HeJ mice, and were not correlated with an activation process as shown by the amount of tumor necrosis factor-alpha (TNF-alpha) being released. Short-time exposure to all stimuli resulted in an increased nucleoside uptake by SAVO pM phi, suggesting that the tumoricidal function of this cell either depends from the type of stimulus or the time when the specific interaction with the cell receptor is taking place. Experiments with priming and triggering signals confirmed the above findings, indicating that the increase or the decrease of nucleoside uptake into the cell depends essentially on the chemical nature of the priming stimulus. The triggering stimulus, on the other hand, is only able to amplify the primary response

  8. Photoelectron and computational studies of the copper-nucleoside anionic complexes, Cu-(cytidine) and Cu-(uridine)

    Science.gov (United States)

    Li, Xiang; Ko, Yeon-Jae; Wang, Haopeng; Bowen, Kit H.; Guevara-García, Alfredo; Martínez, Ana

    2011-02-01

    The copper-nucleoside anions, Cu-(cytidine) and Cu-(uridine), have been generated in the gas phase and studied by both experimental (anion photoelectron spectroscopy) and theoretical (density functional calculations) methods. The photoelectron spectra of both systems are dominated by single, intense, and relatively narrow peaks. These peaks are centered at 2.63 and 2.71 eV for Cu-(cytidine) and Cu-(uridine), respectively. According to our calculations, Cu-(cytidine) and Cu-(uridine) species with these peak center [vertical detachment energy (VDE)] values correspond to structures in which copper atomic anions are bound to the sugar portions of their corresponding nucleosides largely through electrostatic interactions; the observed species are anion-molecule complexes. The combination of experiment and theory also reveal the presence of a slightly higher energy, anion-molecule complex isomer in the case of the Cu-(cytidine). Furthermore, our calculations found that chemically bond isomers of these species are much more stable than their anion-molecule complex counterparts, but since their calculated VDE values are larger than the photon energy used in these experiments, they were not observed.

  9. Photoelectron and computational studies of the copper-nucleoside anionic complexes, Cu(-)(cytidine) and Cu(-)(uridine).

    Science.gov (United States)

    Li, Xiang; Ko, Yeon-Jae; Wang, Haopeng; Bowen, Kit H; Guevara-García, Alfredo; Martínez, Ana

    2011-02-07

    The copper-nucleoside anions, Cu(-)(cytidine) and Cu(-)(uridine), have been generated in the gas phase and studied by both experimental (anion photoelectron spectroscopy) and theoretical (density functional calculations) methods. The photoelectron spectra of both systems are dominated by single, intense, and relatively narrow peaks. These peaks are centered at 2.63 and 2.71 eV for Cu(-)(cytidine) and Cu(-)(uridine), respectively. According to our calculations, Cu(-)(cytidine) and Cu(-)(uridine) species with these peak center [vertical detachment energy (VDE)] values correspond to structures in which copper atomic anions are bound to the sugar portions of their corresponding nucleosides largely through electrostatic interactions; the observed species are anion-molecule complexes. The combination of experiment and theory also reveal the presence of a slightly higher energy, anion-molecule complex isomer in the case of the Cu(-)(cytidine). Furthermore, our calculations found that chemically bond isomers of these species are much more stable than their anion-molecule complex counterparts, but since their calculated VDE values are larger than the photon energy used in these experiments, they were not observed.

  10. Plant nucleoside 5'-phosphoramidate hydrolase; simple purification from yellow lupin (Lupinus luteus) seeds and properties of homogeneous enzyme.

    Science.gov (United States)

    Guranowski, Andrzej; Wojdyła, Anna M; Rydzik, Anna M; Stepiński, Janusz; Jemielity, Jacek

    2011-01-01

    Adenosine 5'-phosphoramidate (NH₂-pA) is an uncommon natural nucleotide of poorly understood biochemistry and function. We studied a plant enzyme potentially involved in the catabolism of NH₂-pA. A fast and simple method comprising extraction of yellow lupin (Lupinus luteus) seed-meal with a low ionic strength buffer, ammonium sulfate and acetone fractionations, removal of contaminating proteins by heat denaturation, and affinity chromatography on AMP-agarose, yielded homogenous nucleoside 5'-phosphoramidase. Mass spectrometric analysis showed that the lupin hydrolase exhibits closest similarity to Arabidopsis thaliana Hint1 protein. The substrate specificity of the lupin enzyme, in particular its ability to split the P-S bond in adenosine 5'-phosphorothioate, is typical of known Hint1 proteins. Adenosine 5'-phosphofluoride and various derivatives of guanosine 5'-phosphoramidate were also substrates. Neither common divalent metal cations nor 10 mM EDTA or EGTA affected the hydrolysis of NH₂-pA. The enzyme functions as a homodimer (2 x 15,800 Da). At the optimum pH of 7.0, the K(m) for NH₂-pA was 0.5 µM and k(cat) 0.8 s⁻¹ (per monomer active site). The properties of the lupin nucleoside 5'-phosphoramidase are compared with those of its counterparts from other organisms.

  11. One-step enzymatic synthesis of nucleosides from low water-soluble purine bases in non-conventional media.

    Science.gov (United States)

    Fernández-Lucas, Jesús; Fresco-Taboada, Alba; de la Mata, Isabel; Arroyo, Miguel

    2012-07-01

    The effect of several water-miscible cosolvents on activity and stability of soluble and immobilized 2'-deoxyribosyltransferase from Lactobacillus reuteri on Sepabeads® has been studied in order to establish optimal conditions for enzymatic synthesis of nucleosides using purine bases with low solubility in aqueous buffer. As a rule of thumb, there was a general reduction of soluble enzyme activity when cosolvent content was gradually increased in reaction medium. In contrast, immobilized enzyme activity was enhanced 1.2-1.4-fold at 20% of methanol, ethanol, 2-propanol, diethylene glycol, and acetone; and at 10% and 30% acetonitrile. Likewise, highest increased activity (1.8-fold) was also obtained in presence of 20% acetonitrile. Immobilized enzyme was successfully used in the synthesis of 2'-deoxyxanthosine and 2'-deoxyguanosine using 2'-deoxyuridine as sugar donor and the corresponding poor water-soluble base in the presence of 30% of methanol, ethanol, 2-propanol, ethylene glycol, acetonitrile, and DMSO, giving high nucleoside yields at 4h. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Simultaneous analysis of nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry.

    Science.gov (United States)

    Huang, Yang; Zhang, Tingting; Zhao, Yumei; Zhou, Haibo; Tang, Guangyun; Fillet, Marianne; Crommen, Jacques; Jiang, Zhengjin

    2017-09-10

    Nucleobases, nucleosides and ginsenosides, which have a significant impact on the physiological activity of organisms, are reported to be the active components of ginseng, while they are less present in ginseng extracts. Few analytical methods have been developed so far to simultaneously analyze these three classes of compounds with different polarities present in ginseng extracts. In the present study, a simple and efficient analytical method was successfully developed for the simultaneous separation of 17 nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry (SFC-MS). The effect of various experimental factors on the separation performance, such as the column type, temperature and backpressure, the type of modifier and additive, and the concentration of make-up solvent were systematically investigated. Under the selected conditions, the developed method was successfully applied to the quality evaluation of 14 batches of ginseng extracts from different origins. The results obtained for the different batches indicate that this method could be employed for the quality assessment of ginseng extracts. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates

    Directory of Open Access Journals (Sweden)

    Shainberg Asher

    2008-10-01

    Full Text Available Abstract Background An approach to use multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors (GPCRs was recently introduced. Results A known adenosine receptor (AR agonist was conjugated to polyamidoamine (PAMAM dendrimer carriers for delivery of the intact covalent conjugate to on the cell surface. Depending on the linking moiety, multivalent conjugates of the N6-chain elongated functionalized congener ADAC (N6-[4-[[[4-[[[(2-aminoethylamino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl]-adenosine achieved unanticipated high selectivity in binding to the cytoprotective human A3 AR, a class A GPCR. The key to this selectivity of > 100-fold in both radioreceptor binding (Ki app = 2.4 nM and functional assays (EC50 = 1.6 nM in inhibition of adenylate cyclase was maintaining a free amino group (secondary in an amide-linked chain. Attachment of neutral amide-linked chains or thiourea-containing chains preserved the moderate affinity and efficacy at the A1 AR subtype, but there was no selectivity for the A3 AR. Since residual amino groups on dendrimers are associated with cytotoxicity, the unreacted terminal positions of this A3 AR-selective G2.5 dendrimer were present as carboxylate groups, which had the further benefit of increasing water-solubility. The A3 AR selective G2.5 dendrimer was also visualized binding the membrane of cells expressing the A3 receptor but did not bind cells that did not express the receptor. Conclusion This is the first example showing that it is feasible to modulate and even enhance the pharmacological profile of a ligand of a GPCR based on conjugation to a nanocarrier and the precise structure of the linking group, which was designed to interact with distal extracellular regions of the 7 transmembrane-spanning receptor. This ligand tool can now be used in pharmacological models of tissue rescue from ischemia and to probe the existence of A3 AR

  14. Carbon-14 labelling of biomolecules induced by 14CO ionized gas

    International Nuclear Information System (INIS)

    Lier, J.E. van; Sanche, L.

    1979-01-01

    Ionized 14 CO gas provides a rapid method for producing 14 C-labelled biomolecules. The apparatus consists of a high vacuum system in which a small amount of 14 CO is ionized by electron impact. The resulting species drift towards a target where they interact with the molecule of interest to produce 14 C-labelled compounds. Since the reaction time is only 2 minutes, the method is particularly promising for producing tracer biomolecules with short-lived 11 C at high specific activities. The applicability of the method to various classes of compounds of biological importance, including steroids, alkaloids, prostaglandins, nucleosides, amino acids and proteins has been studied. All compounds treated gave rise to 14 C addition and degradation products. Furthermore, for some compounds, chromatographic analysis in multiple systems followed by derivatization and crystallization to constant specific activity, indicated that carbon exchange may occur to produce the labelled, but otherwise unaltered substrate in yields of the order of 10-100 mCi/mol. More conclusive proof of radiochemical identity must await production of larger quantities of material and rigorous purification including at least two different chromatographic techniques. (author)

  15. Modeling the effects of labeling

    DEFF Research Database (Denmark)

    Juhl, Hans Jørn; Fjord, Thomas Ahle; Poulsen, Carsten Stig

    A new approach to evaluate the consequences of labeling is presented and applied to test the potential effect of a label on fresh fish. Labeling effects on quality perceptions and overall quality are studied. The empirical study is based on an experimental design and nearly 500 respondents...

  16. Isotopically labelled benzodiazepines

    International Nuclear Information System (INIS)

    Liebman, A.A.

    1987-01-01

    This paper reports on the benzodiazepines which are a class of therapeutic agents. Improvements in the analytical methodology in the areas of biochemistry and pharmacology were significant, particularly in the application of chromatographic and spectroscopic techniques. In addition, the discovery and subsequent development of tritium and carbon-14 as an analytical tool in the biological sciences were essentially post-world war II phenomena. Thus, as these new chemical entities were found to be biologically active, they could be prepared in labeled form for metabolic study, biological half-life determination (pharmacokinetics), tissue distribution study, etc. This use of tracer methodology has been liberally applied to the benzodiazepines and also more recently to the study of receptor-ligand interactions, in which tritium, carbon-11 or fluorine-18 isotopes have been used. The history of benzodiazepines as medicinal agents is indeed an interesting one; an integral part of that history is their use in just about every conceivable labeled form

  17. Ferrocene-functionalized graphitic carbon nitride as an enhanced heterogeneous catalyst of Fenton reaction for degradation of Rhodamine B under visible light irradiation.

    Science.gov (United States)

    Lin, Kun-Yi Andrew; Lin, Jyun-Ting

    2017-09-01

    To enhance degradation of Rhodamine B (RhB), a toxic xanthene dye, an iron-doped graphitic carbon nitride (CN) is prepared by establishing a covalent bond (-CN-) bridging ferrocene (Fc) and CN via a Schiff base reaction. The π-conjugation between the aromatic Fc and CN can be much enhanced by the covalent bond, thereby facilitating the bulk-to-surface charge transfer and separation as well as reversible photo-redox reactions during photocatalytic reactions. Thus, the resulting Fc-CN exhibits a much higher catalytic activity than CN to activate hydrogen peroxide (HP) for RhB degradation, because the photocatalytically generated electrons from CN can activate HP and effectively maintain the bivalence state of Fe in Fc, which also induces the activation of HP. The RhB degradation by the Fc-CN activated HP process (Fc-CN-HP) is validated to involve OH • by examining the effect of radical probe agent as well as electron paramagnetic resonance (EPR) spectroscopic analysis. Fc-CN is also proven to activate HP for RhB degradation over multiple times without loss of catalytic activity. Through determining the degradation intermediates, RhB is indeed fully decomposed by Fc-CN-HP into much lower-molecular-weight organic compounds. These features indicate that Fc-functionalization can be an advantageous technique to enhance the catalytic activity of CN for activating HP. The results obtained in this study are essential to further design and utilize Fc-functionalized CN for Fenton-like reactions. The findings shown here, especially the degradation mechanism and pathway, are also quite important for treating xanthene dyes in wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Gold(I) complex of 1,1'-bis(diphenylphosphino) ferrocene-quinoline conjugate: a virostatic agent against HIV-1.

    Science.gov (United States)

    Gama, Ntombenhle; Kumar, Kamlesh; Ekengard, Erik; Haukka, Matti; Darkwa, James; Nordlander, Ebbe; Meyer, Debra

    2016-06-01

    HIV infection is known for replicating in proliferating CD(+) T-cells. Treatment of these cells with cytostatic (anti-proliferation) compounds such as hydroxyurea interferes with the cells's ability support HIV replication. Combinations of such cytostatic compounds with proven anti-retroviral drugs (like ddI) are known as virostatic, and have been shown to aid in the control of the infection. The use of two different drugs in virostatic combinations however, carries the risk of adverse effects including drug-drug interactions, which could lead to augmented toxicities and reduced efficacy. Here, a novel digold(I) complex of ferrocene-quinoline (3) was investigated for cytostatic behaviour as well as anti-viral activity which if demonstrated would eliminate concerns of drug-drug interactions. The complex was synthesized and characterized by NMR, FT-IR and mass spectroscopy and the molecular structure was confirmed by X-ray crystallography. Bio-screening involved viability dyes, real time electronic sensing and whole virus assays. The complex showed significant (p = 0.0092) inhibition of virus infectivity (83 %) at 10 ug/mL. This same concentration caused cytostatic behaviour in TZM-bl cells with significant (p < 0.01) S and G2/M phase cell cycle arrest. These data supports 3 as a virostatic agent, possessing both anti-viral and cytostatic characteristics. In the absence of 3, TZM-bl cells were infected by a pseudovirus and this was demonstrated through luminescence in a luciferase assay. Pre-incubation of the virus with 3 decreased luminescence, indicating the anti-viral activity of 3. Complex 3 also showed cytostatic behavior with increased S-phase and G2/M phase cell cycle arrest.

  19. Review of nutrition labeling formats.

    Science.gov (United States)

    Geiger, C J; Wyse, B W; Parent, C R; Hansen, R G

    1991-07-01

    This article examines nutrition labeling history as well as the findings of nine research studies of nutrition labeling formats. Nutrition labeling regulations were announced in 1973 and have been periodically amended since then. In response to requests from consumers and health care professionals for revision of the labeling system, the Food and Drug Administration initiated a three-phase plan for reform of nutrition labeling in 1990. President Bush signed the Nutrition Labeling and Education Act in November 1990. Literature analysis revealed that only nine studies with an experimental design have focused on nutrition labeling since 1971. Four were conducted before 1975, which was the year that nutrition labeling was officially implemented, two were conducted in 1980, and three were conducted after 1986. Only two of the nine studies supported the traditional label format mandated by the Code of Federal Regulations, and one study partially supported it. Four of the nine studies that evaluated graphic presentations of nutrition information found that consumer comprehension of nutrition information was improved with a graphic format for nutrition labeling: three studies supported the use of bar graphs and one study supported the use of a pie chart. Full disclosure (ie, complete nutrient and ingredient labeling) was preferred by consumers in two of the three studies that examined this variable. The third study supported three types of information disclosure dependent upon socioeconomic class. In those studies that tested graphics, a bar graph format was significantly preferred and showed better consumer comprehension than the traditional format.

  20. Linerless label device and method

    KAUST Repository

    Binladen, Abdulkari

    2016-01-14

    This apparatus and method for applying a linerless label to an end user product includes a device with a printer for printing on a face surface of a linerless label, and a release coat applicator for applying a release coat to the face surface of the label; another device including an unwinder unit (103) to unwind a roll of printed linerless label; a belt (108); a glue applicator (102) for applying glue to the belt; a nip roller (106) for contacting and applying pressure to the face surface of the linerless label such that the glue on the belt transfers to the back surface of the linerless label; at least one slitting knife 105) positioned downstream the belt and a rewinder unit (104) positioned downstream the slitting knife; and a third device which die cuts and applies the linerless label to an end user object.

  1. Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism

    Czech Academy of Sciences Publication Activity Database

    Downey, Alan Michael; Pohl, Radek; Roithová, J.; Hocek, Michal

    2017-01-01

    Roč. 23, č. 16 (2017), s. 3910-3917 ISSN 0947-6539 R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA16-00178S Institutional support: RVO:61388963 Keywords : epoxides * glycosylation * nucleosides * riboses * synthesis design Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 5.317, year: 2016

  2. Synthesis and Evaluation of the Biological Profile of Novel Analogues of Nucleosides and of Potential Mimetics of Sugar Phosphates and Nucleotides

    Czech Academy of Sciences Publication Activity Database

    Xavier, N.M.; Lucas, S.D.; Jorda, Radek; Schwarz, S.; Loesche, A.; Csuk, R.; Oliveira, M.C.

    2015-01-01

    Roč. 26, č. 19 (2015), s. 2663-2672 ISSN 0936-5214 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : nucleosides * nucleotides * carbohydrates Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.323, year: 2015

  3. Cytostatic 6-arylpurine nucleosides III. Synthesis and structure-activity relationship study in cytostatic activity of 6-aryl-, 6-hetaryl- and 6-benzylpurine ribonucleosides

    Czech Academy of Sciences Publication Activity Database

    Hocek, Michal; Holý, Antonín; Votruba, Ivan; Dvořáková, H.

    2001-01-01

    Roč. 66, č. 3 (2001), s. 483-499 ISSN 0010-0765 R&D Projects: GA ČR GV203/96/K001; GA ČR GA203/00/0036 Institutional research plan: CEZ:AV0Z4055905 Keywords : purines * nucleosides Subject RIV: CC - Organic Chemistry Impact factor: 0.778, year: 2001

  4. Synthesis of novel carbocyclic nucleosides and Pro-Tides derived from 4-oxatricyclo[4.2.1.03,7]nonane-9-methanol

    Czech Academy of Sciences Publication Activity Database

    Hřebabecký, Hubert; Dračínský, Martin; Holý, Antonín

    2007-01-01

    Roč. 72, č. 10 (2007), s. 1331-1349 ISSN 0010-0765 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Institutional research plan: CEZ:AV0Z40550506 Keywords : carbocyclic nucleosides * purines * thymine Subject RIV: CC - Organic Chemistry Impact factor: 0.879, year: 2007

  5. Cooperation and competition between adenylate kinase, nucleoside diphosphokinase, electron transport, and ATP synthase in plant mitochondria studied by 31P-nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Roberts, J.K.M.; Aubert, S.; Gout, E.; Bligny, R.; Douce, R.

    1997-01-01

    Nucleotide metabolism in potato (Solanum tuberosum) mitochondria was studied using 31P-nuclear magnetic resonance spectroscopy and the O2 electrode. Immediately following the addition of ADP, ATP synthesis exceeded the rate of oxidative phosphorylation, fueled by succinate oxidation, due to mitochondrial adenylate kinase (AK) activity two to four times the maximum activity of ATP synthase. Only when the AK reaction approached equilibrium was oxidative phosphorylation the primary mechanism for net ATP synthesis. A pool of sequestered ATP in mitochondria enabled AK and ATP synthase to convert AMP to ATP in the presence of exogenous inorganic phosphate. During this conversion, AK activity can indirectly influence rates of oxidation of both succinate and NADH via changes in mitochondrial ATP. Mitochondrial nucleoside diphosphokinase, in cooperation with ATP synthase, was found to facilitate phosphorylation of nucleoside diphosphates other than ADP at rates similar to the maximum rate of oxidative phosphorylation. These results demonstrate that plant mitochondria contain all of the machinery necessary to rapidly regenerate nucleoside triphosphates from AMP and nucleoside diphosphates made during cellular biosynthesis and that AK activity can affect both the amount of ADP available to ATP synthase and the level of ATP regulating electron transport

  6. Hydrophilic interaction ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry for determination of nucleotides, nucleosides and nucleobases in Ziziphus plants.

    Science.gov (United States)

    Guo, Sheng; Duan, Jin-ao; Qian, Dawei; Wang, Hanqing; Tang, Yuping; Qian, Yefei; Wu, Dawei; Su, Shulan; Shang, Erxin

    2013-08-02

    In this study, a rapid and sensitive analytical method was developed for the determination of 20 nucleobases, nucleosides and nucleotides in Ziziphus plants at trace levels by using hydrophilic interaction ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC-UHPLC-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode. Under the optimized chromatographic conditions, good separation for 20 target compounds were obtained on a UHPLC Amide column with sub-2μm particles within 10min. The overall LODs and LOQs were between 0.11-3.12ngmL(-1) and 0.29-12.48ngmL(-1) for the 20 analytes, respectively. It is the first report about simultaneous analysis of nucleobases, nucleosides and nucleotides in medicinal plants using HILIC-UHPLC-TQ-MS/MS method, which affords good linearity, precision, repeatability and accuracy. The developed method was successfully applied to Ziziphus plant (Z. jujuba, Z. jujuba var. spinosa and Z. mauritiana) samples. The analysis showed that the fruits and leaves of Ziziphus plants are rich in nucleosides and nucleobases as well as nucleotides, and could be selected as the healthy food resources. Our results in present study suggest that HILIC-UHPLC-TQ-MS/MS method could be employed as a useful tool for quality assessment of the samples from the Ziziphus plants as well as other medicinal plants or food samples using nucleotides, nucleosides and nucleobases as markers. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses

    NARCIS (Netherlands)

    I. Deuzing (Ilona); C. Charpentier (Charlotte); D.J. Wright (David Justin); S. Matheron (Sophie); J. Paton (Jack); D. Frentz (Dineke); D.A.M.C. van de Vijver (David); P.V. Coveney (Peter); D. Descamps (Diane); C.A.B. Boucher (Charles); N. Beerens (Nancy)

    2015-01-01

    textabstractInfection with HIV-2 can ultimately lead to AIDS, although disease progression is much slower than with HIV-1. HIV-2 patients are mostly treated with a combination of nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and protease inhibitors designed for HIV-1. Many studies have

  8. Establishment of New Transmissible and Drug-Sensitive Human Immunodeficiency Virus Type 1 Wild Types due to Transmission of Nucleoside Analogue-Resistant Virus

    NARCIS (Netherlands)

    Ronde, Anthony de; Dooren, Maaike van; Hoek, Lian van der; Bouwhuis, Denise; Rooij, Esther de; Gemen, Bob van; Boer, R.J. de; Goudsmit, Jaap

    2000-01-01

    Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT).

  9. Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus

    NARCIS (Netherlands)

    de Ronde, A.; van Dooren, M.; van der Hoek, L.; Bouwhuis, D.; de Rooij, E.; van Gemen, B.; de Boer, R.; Goudsmit, J.

    2001-01-01

    Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT).

  10. Co- and homocyclotrimerization reactions of protected 1-alkynyl-2-deoxyribofuranose. Synthesis of C-nucleosides, C-di- and C-trisaccharide analogues

    Czech Academy of Sciences Publication Activity Database

    Novák, P.; Číhalová, S.; Otmar, Miroslav; Hocek, Michal; Kotora, Martin

    2008-01-01

    Roč. 64, č. 22 (2008), s. 5200-5207 ISSN 0040-4020 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : alkynes * cyclotrimerizations * nucleosides Subject RIV: CC - Organic Chemistry Impact factor: 2.897, year: 2008

  11. Characterisation of nucleosides and nucleobases in Mactra veneriformis by high performance liquid chromatography coupled with diode array detector-mass spectrometry (HPLC-DAD-MS).

    Science.gov (United States)

    Liu, Rui; Ji, Jing; Wang, Lingchong; Chen, Shiyong; Guo, Sheng; Wu, Hao

    2012-11-15

    Mactra veneriformis has been used as sea food and traditional Chinese medicine (TCM) for thousands of years in China. In the present study, a high performance liquid chromatograph coupled with photodiode array detector and electrospray ionisation-mass spectrometer (HPLC-DAD-ESI-MS) method was established for detection of the nucleosides and nucleobases in M. veneriformis from four aquaticultural area of Jiangsu during different harvest time of one year. The validated method was successfully applied to identifying 10 nucleosides and nucleobases in 48 M. veneriformis samples. Quantitative analysis showed that nucleosides and nucleobases are rich in all M. veneriformis samples. However, their contents vary in different areas and harvest times. Principal component analysis (PCA) was used to classify the 48 samples based on the contents of the nucleosides and nucleobases. As a result, the samples could be mainly clustered into four groups, which was similar as aquaticultural areas classification. Based on the results, present method might be applicable for the quality control of M. veneriformis, or even other marine shellfish aquiculture and their products, and the quality of M. veneriformis might be more related with aquaticultural areas. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl) methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1

    Czech Academy of Sciences Publication Activity Database

    Šimon, Petr; Baszczyňski, Ondřej; Šaman, David; Stepan, G.; Hu, E.; Lansdon, E. B.; Jansa, P.; Janeba, Zlatko

    2016-01-01

    Roč. 122, Oct 21 (2016), s. 185-195 ISSN 0223-5234 Institutional support: RVO:61388963 Keywords : diarylpyrimidine (DAPY) * etravirine * human immunodeficiency virus ( HIV ) * non-nucleoside reverse transcriptase inhibitors * NNRTIs * rilpivirine Subject RIV: CC - Organic Chemistry Impact factor: 4.519, year: 2016

  13. Synthesis of 2'-deoxyadenosine nucleosides bearing bipyridine-type ligands and their Ru-complexes in position 8 through cross-coupling reactions

    Czech Academy of Sciences Publication Activity Database

    Vrábel, Milan; Pohl, Radek; Klepetářová, Blanka; Votruba, Ivan; Hocek, Michal

    2007-01-01

    Roč. 5, č. 17 (2007), s. 2849-2857 ISSN 1477-0520 R&D Projects: GA MŠk LC512; GA ČR GA203/05/0043 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * purines * cross-coupling * ruthenium Subject RIV: CC - Organic Chemistry Impact factor: 3.167, year: 2007

  14. Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1)

    Czech Academy of Sciences Publication Activity Database

    Zouharová, D.; Lipenská, I.; Fojtiková, M.; Kulich, P.; Neca, J.; Slaný, M.; Kovařčík, K.; Turanek-Knotigová, P.; Hubatka, F.; Celechovská, H.; Mašek, J.; Koudelka, Š.; Procházka, L.; Eyer, L.; Plocková, J.; Bartheldyová, E.; Miller, A. D.; Růžek, Daniel; Raška, M.; Janeba, Zlatko; Turánek, J.

    2016-01-01

    Roč. 184, FEB 29 (2016), s. 84-93 ISSN 0378-1135 Institutional support: RVO:60077344 ; RVO:61388963 Keywords : Pseudorabies * Acyclic nucleoside phosphonates * DNA viruses * Cidofovir * Antiviral drugs * DNA polymerase Subject RIV: EE - Microbiology, Virology; CC - Organic Chemistry (UOCHB-X) Impact factor: 2.628, year: 2016

  15. Sugar-modified derivatives of cytostatic 6-(het)aryl-7-deazapurine nucleosides: 2'-C-methylribonucleosides, arabinonucleosides and 2'-deoxy-2'-fluoroarabinonucleosides

    Czech Academy of Sciences Publication Activity Database

    Nauš, Petr; Perlíková, Pavla; Pohl, Radek; Hocek, Michal

    2011-01-01

    Roč. 76, č. 8 (2011), s. 957-988 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleosides * cross - coupling * antitumor agents * purines * 7-deazapurines * 7H-Pyrrolo[2,3d]pyrimidine * cytostatic agents Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  16. Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.

    Science.gov (United States)

    Egeblad, Louise; Welin, Martin; Flodin, Susanne; Gräslund, Susanne; Wang, Liya; Balzarini, Jan; Eriksson, Staffan; Nordlund, Pär

    2012-01-01

    To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of "off target effects." However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA) and uridine phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔT(agg) around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design.

  17. A quantitative histochemical procedure for the demonstration of purine nucleoside phosphorylase activity in rat and human liver using Tetranitro BT and xanthine oxidase as auxiliary enzyme

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.; van Gulik, T.

    1993-01-01

    A quantitative histochemical procedure was developed for the demonstration of purine nucleoside phosphorylase in rat liver using unfixed cryostat sections and the auxiliary enzyme xanthine oxidase. The optimum incubation medium contained 18% (w/v) poly(vinyl alcohol), 100 mM phosphate buffer, pH

  18. Method of preparing highly active and thermostable preparations of liver uridin-kinase usable for enzymic synthesis of radioactive nucleoside-5'-phosphates

    International Nuclear Information System (INIS)

    Cihak, A.; Vesely, J.

    1975-01-01

    A method is described of preparing a high-activity uridine kinase for the enzymic synthesis of radioactive nucleoside-5m-phosphates of the pyrimidine series. The preparation is separated from male rat liver after intraperitoneal application of 5'-azacytidine. Examples are given showing detailed procedures for the conversion of uridine and 6-azauridine to the corresponding 5'-phosphates. (L.K.)

  19. Aqueous Heck Cross-Coupling Preparation of Acrylate-Modified Nucleotides and Nucleoside Triphosphates for Polymerase Synthesis of Acrylate-Labeled DNA

    Czech Academy of Sciences Publication Activity Database

    Daďová, Jitka; Vidláková, Pavlína; Pohl, Radek; Havran, Luděk; Fojta, Miroslav; Hocek, Michal

    2013-01-01

    Roč. 78, č. 19 (2013), s. 9627-9637 ISSN 0022-3263 R&D Projects: GA AV ČR(CZ) IAA400040901 Institutional support: RVO:61388963 ; RVO:68081707 Keywords : nucleic-acids * enzymatic incorporation * protein interactions * functionalized DNA Subject RIV: CC - Organic Chemistry Impact factor: 4.638, year: 2013

  20. Labelled compounds. (Pt. B)

    International Nuclear Information System (INIS)

    Buncel, E.; Jones, J.R.

    1991-01-01

    Since the end of World War II there has been a tremendous increase in the number of compounds that have been synthesized with radioactive or stable isotopes. They have found application in many diverse fields, so much so, that hardly a single area in pure and applied science has not benefited. Not surprisingly it has been reflected in appearance of related publications. The early proceedings of the Symposia on Advances in Trace Methodology were soon followed by various Euratom sponsored meetings in which methods of preparing and storing labelled compounds featured prominently. In due course a resurgence of interest in stable isotopes, brought about by their greater availability (also lower cost) and partly by development of new techniques such as gas chromatography - mass spectrometry (gc-ms), led to the publication of proceedings of several successful conferences. More recently conferences dealing with the synthesis and applications of isotopes and isotopically labelled compounds have been established on a regular basis. In addition to the proceedings of conferences and journal publications individuals left their mark by producing definitive texts, usually on specific nuclides. Only the classic two volume publication of Murray and Williams (Organic syntheses with isotopes, New York 1985), now over 30 years old and out of print, attempted to do justice to several nuclides. With the large amount of work that has been undertaken since then it seems unlikely that an updated edition could be produced. The alternative strategy was to ask scientists currently active to review specific areas and this is the approach adopted in the present series of monographs. In this way it is intended to cover the broad advances that have been made in the synthesis and applications of isotopes and isotopically labelled compounds in the physical and biomedical sciences. (author). refs.; figs.; tabs

  1. From Label to Practice

    DEFF Research Database (Denmark)

    Byrkjeflot, Haldor; Strandgaard, Jesper; Svejenova, Silviya

    2013-01-01

    because NNC was conceived as an identity movement, triggered by active involvement of entrepreneurial leaders from the culinary profession, high-profile political supporters, legitimating scientists, disseminating media, and interpreting audiences. It was facilitated by three mechanisms: First, the use......This article examines the process of creation of new Nordic cuisine (NNC) as a culinary innovation, focusing on the main stages, actors, and mechanisms that shaped the new label and its practices and facilitated its diffusion in the region and internationally. Fast-paced diffusion was possible...

  2. The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects.

    Science.gov (United States)

    Ruane, P J; Brinson, C; Ramgopal, M; Ryan, R; Coate, B; Cho, M; Kakuda, T N; Anderson, D

    2015-05-01

    Following antiretroviral therapy failure, patients are often treated with a three-drug regimen that includes two nucleoside/tide reverse transcriptase inhibitors [N(t)RTIs]. An alternative two-drug nucleoside-sparing regimen may decrease the pill burden and drug toxicities associated with the use of N(t)RTIs. The Intelence aNd pRezista Once A Day Study (INROADS; NCT01199939) evaluated the nucleoside-sparing regimen of etravirine 400 mg with darunavir/ritonavir 800/100 mg once-daily in HIV-1-infected treatment-experienced subjects or treatment-naïve subjects with transmitted resistance. In this exploratory phase 2b, single-arm, open-label, multicentre, 48-week study, the primary endpoint was the proportion of subjects who achieved HIV-1 RNA treatment-experienced subjects or treatment-naïve subjects with transmitted resistance was virologically efficacious and well tolerated. © 2014 British HIV Association.

  3. Label and Label-Free Detection Techniques for Protein Microarrays

    Directory of Open Access Journals (Sweden)

    Amir Syahir

    2015-04-01

    Full Text Available Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano‑biological events.

  4. Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble[(3,5,5-Trimethylhexanoyl)ferrocene

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan

    2007-01-01

    Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (......, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.......Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl......)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of a- and ¿-tocopherols and glutathione (GSH) were also higher. In contrast, the brain...

  5. Synthesis of silylated pyrimidines nucleosides. Catalytic condensations with organo-zinc, organo-zirconium, and organo-borane compounds

    International Nuclear Information System (INIS)

    Vincent, Patrice

    1982-01-01

    This research thesis addressed the synthesis of new desoxy-2' uridines substituted in C-5. The starting compound was the iodo-5 0-3',5' bis(trimethylsilyl) dUrd. It has been coupled with acetylenic organo-zinc in presence of organo-palladium and nickel compounds to obtain alkynyl-5 dUrd, with ethylenic organo-zirconium compounds in presence of organo-palladium complexes to obtain (E)-alkenyl-5 dUrd, with ethylenic organo-boranes in presence of organo-palladium complexes to obtain (E) and (Z) alkenyl-5 uRd, and with cyclic or heterocyclic organo-zinc compounds in presence of organo-palladium complexes. Thirty new pyrimidine nucleosides have thus been obtained, and some of them have been used for biological tests [fr

  6. Separation of oligopeptides, nucleobases, nucleosides and nucleotides using capillary electrophoresis/electrochromatography with sol-gel modified inner capillary wall.

    Science.gov (United States)

    Svobodová, Jana; Kofroňová, Olga; Benada, Oldřich; Král, Vladimír; Mikšík, Ivan

    2017-09-29

    The aim of this article is to study the modification of an inner capillary wall with sol-gel coating (pure silica sol-gel or silica sol-gel containing porphyrin-brucine conjugate) and determine its influence on the separation process using capillary electrophoresis/electrochromatography method. After modification of the inner capillary surface the separation of analytes was performed using two different phosphate buffers (pH 2.5 and 9.0) and finally the changes in electrophoretic mobilities of various samples were calculated. To confirm that the modification of the inner capillary surface was successful, the parts of the inner surfaces of capillaries were observed using scanning electron microscopy. The analytes used as testing samples were oligopeptides, nucleosides, nucleobases and finally nucleotides. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Contents Changes of Triterpenic Acids, Nucleosides, Nucleobases, and Saccharides in Jujube (Ziziphus jujuba) Fruit During the Drying and Steaming Process.

    Science.gov (United States)

    Guo, Sheng; Duan, Jin-Ao; Zhang, Ying; Qian, Dawei; Tang, Yuping; Zhu, Zhenhua; Wang, Hanqing

    2015-12-12

    Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of triterpenic acids, nucleosides, nucleobases and saccharides after drying and steaming treatment were determined using ultra-high performance liquid chromatography and high performance liquid chromatography coupled with evaporative light scattering detector methods. The results showed that except for sucrose, the content levels of most analytes were increasing in the jujube fruits during drying treatment at 45 °C. The levels of cyclic nucleotides such as adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, were significantly decreased after the fruits were steamed. Therefore, owing to the bioactivities of these components for human health, the dried fruits would be the better choice as medicinal material or functional food, and dried jujube fruit should not be further steamed.

  8. Distance labeling schemes for trees

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Gørtz, Inge Li; Bistrup Halvorsen, Esben

    2016-01-01

    We consider distance labeling schemes for trees: given a tree with n nodes, label the nodes with binary strings such that, given the labels of any two nodes, one can determine, by looking only at the labels, the distance in the tree between the two nodes. A lower bound by Gavoille et al. [Gavoille...... variants such as, for example, small distances in trees [Alstrup et al., SODA, 2003]. We improve the known upper and lower bounds of exact distance labeling by showing that 1/4 log2(n) bits are needed and that 1/2 log2(n) bits are sufficient. We also give (1 + ε)-stretch labeling schemes using Theta...

  9. Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization

    Science.gov (United States)

    Mishra, Arjun K.; Singh, Nidhi; Agnihotri, Pragati; Mishra, Shikha; Singh, Saurabh P.; Kolli, Bala K.; Chang, Kwang Poo; Sahasrabuddhe, Amogh A.; Siddiqi, M. I.; Pratap, J. Venkatesh

    2017-06-01

    Nucleoside diphosphate kinases (NDKs) are ubiquitous enzymes that catalyze the transfer of the γ-phosphate moiety from an NTP donor to an NDP acceptor, crucial for maintaining the cellular level of nucleoside triphosphates (NTPs). The inability of trypanosomatids to synthesize purines de novo and their dependence on the salvage pathway makes NDK an attractive target to develop drugs for the diseases they cause. Here we report the discovery of novel inhibitors for Leishmania NDK based on the structural and functional characterization of purified recombinant NDK from Leishmania amazonensis. Recombinant LaNDK possesses auto-phosphorylation, phosphotransferase and kinase activities with Histidine 117 playing an essential role. LaNDK crystals were grown by hanging drop vapour diffusion method in a solution containing 18% PEG-MME 500, 100 mM Bis-Tris propane pH 6.0 and 50 mM MgCl2. It belongs to the hexagonal space group P6322 with unit cell parameters a = b = 115.18, c = 62.18 Å and α = β = 90°, γ = 120°. The structure solved by molecular replacement methods was refined to crystallographic R-factor and Rfree values of 22.54 and 26.52%, respectively. Molecular docking and dynamics simulation -based virtual screening identified putative binding compounds. Protein inhibition studies of selected hits identified five inhibitors effective at micromolar concentrations. One of the compounds showed 45% inhibition of Leishmania promastigotes proliferation. Analysis of inhibitor-NDK complexes reveals the mode of their binding, facilitating design of new compounds for optimization of activities as drugs against leishmaniasis.

  10. Metabolomic profile and nucleoside composition of Cordyceps nidus sp. nov. (Cordycipitaceae: A new source of active compounds.

    Directory of Open Access Journals (Sweden)

    Juan Chiriví

    Full Text Available Cordyceps sensu lato is a genus of arthropod-pathogenic fungi, which have been used traditionally as medicinal in Asia. Within the genus, Ophiocordyceps sinensis is the most coveted and expensive species in China. Nevertheless, harvesting wild specimens has become a challenge given that natural populations of the fungus are decreasing and because large-scale culture of it has not yet been achieved. The worldwide demand for products derived from cultivable fungal species with medicinal properties has increased recently. In this study, we propose a new species, Cordyceps nidus, which parasitizes underground nests of trapdoor spiders. This species is phylogenetically related to Cordyceps militaris, Cordyceps pruinosa, and a sibling species of Cordyceps caloceroides. It is found in tropical rainforests from Bolivia, Brazil, Colombia and Ecuador. We also investigated the medicinal potential of this fungus based on its biochemical properties when grown on four different culture media. The metabolic profile particularly that of nucleosides, in polar and non-polar extracts was determined by UPLC, and then correlated to their antimicrobial activity and total phenolic content. The metabolome showed a high and significant dependency on the substrate used for fungal growth. The mass intensities of nucleosides and derivative compounds were higher in natural culture media in comparison to artificial culture media. Among these compounds, cordycepin was the predominant, showing the potential use of this species as an alternative to O. sinensis. Furthermore, methanol fractions showed antimicrobial activity against gram-positive bacteria, and less than 3.00 mg of gallic acid equivalents per g of dried extract were obtained when assessing its total phenolic content by modified Folin-Ciocalteu method. The presence of polyphenols opens the possibility of further exploring the antioxidant capacity and the conditions that may enhance this characteristic. The metabolic

  11. Co-Labeling for Multi-View Weakly Labeled Learning.

    Science.gov (United States)

    Xu, Xinxing; Li, Wen; Xu, Dong; Tsang, Ivor W

    2016-06-01

    It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co-labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo-label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi

  12. The radioactive labeling of monocytes

    International Nuclear Information System (INIS)

    Ensing, G.J.

    1985-01-01

    With the aim of studying a possible relationship between circulating monocytes and Sternberg-Reed cells investigations were started on the specific labeling of monocytes. In this thesis the literature on the pertinent data has been reviewed and a series of experiments on the monocyte labeling procedure has been described. The principles of cell labeling with radioactive compounds were discussed. 1. Total separation of the particular cell population to be labeled and subsequent labeling with a non-specific radiopharmaceutical. 2. Specific cell labeling in a mixture of cell types based on a well defined affinity of the cell under study for the radiopharmaceutical used. Next the radionuclides that can be used for cell labeling purposes were discussed with special attention for 111 In and its chelates. The principles of radiodosimetry were also discussed shortly. This section was focussed on the radiation dose the labeled cells receive because of the intracellular localized radioactivity. The radiation burden is high in comparison to amounts of radiation known to affect cell viability. A newly developed method for labeling monocytes specifically by phagocytosis of 111 In-Fe-colloid without apparent loss of cells was described in detail. (Auth.)

  13. Labelled molecules, modern research implements

    International Nuclear Information System (INIS)

    Pichat, L.; Langourieux, Y.

    1974-01-01

    Details of the synthesis of carbon 14- and tritium-labelled molecules are examined. Although the methods used are those of classical organic chemistry the preparation of carbon 14-labelled molecules differs in some respects, most noticeably in the use of 14 CO 2 which requires very special handling techniques. For the tritium labelling of organic molecules the methods are somewhat different, very often involving exchange reactions. The following are described in turn: the so-called Wilzbach exchange method; exchange by catalysis in solution; catalytic hydrogenation with tritium; reductions with borotritides. Some applications of labelled molecules in organic chemistry, biochemistry and pharmacology are listed [fr

  14. Radioactive decay and labeled compounds

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    This chapter on radioactive decay and labeled compounds has numerous intext equations and worked, sample problems. Topics covered include the following: terms and mathematics of radioactive decay; examples of calculations; graphs of decay equations; radioactivity or activity; activity measurements; activity decay; half-life determinations; labeled compounds. A 20 problem set is also included. 1 ref., 4 figs., 1 tab

  15. Linerless label device and method

    KAUST Repository

    Binladen, Abdulkari

    2016-01-01

    This apparatus and method for applying a linerless label to an end user product includes a device with a printer for printing on a face surface of a linerless label, and a release coat applicator for applying a release coat to the face surface

  16. Nutrition Marketing on Food Labels

    Science.gov (United States)

    Colby, Sarah E.; Johnson, LuAnn; Scheett, Angela; Hoverson, Bonita

    2010-01-01

    Objective: This research sought to determine how often nutrition marketing is used on labels of foods that are high in saturated fat, sodium, and/or sugar. Design and Setting: All items packaged with food labels (N = 56,900) in all 6 grocery stores in Grand Forks, ND were surveyed. Main Outcome Measure(s): Marketing strategy, nutrient label…

  17. 21 CFR 201.70 - Calcium labeling.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Calcium labeling. 201.70 Section 201.70 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.70 Calcium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the calcium content per...

  18. 49 CFR 172.450 - EMPTY label.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false EMPTY label. 172.450 Section 172.450... SECURITY PLANS Labeling § 172.450 EMPTY label. (a) Each EMPTY label, except for size, must be as follows....) in height. (2) The label must be white with black printing. (b) [Reserved] ...

  19. 21 CFR 610.60 - Container label.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Container label. 610.60 Section 610.60 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.60 Container label. (a) Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a full...

  20. 49 CFR 172.442 - CORROSIVE label.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false CORROSIVE label. 172.442 Section 172.442... SECURITY PLANS Labeling § 172.442 CORROSIVE label. (a) Except for size and color, the CORROSIVE label must... CORROSIVE label must be white in the top half and black in the lower half. [Amdt. 172-123, 56 FR 66259, Dec...