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Sample records for acyclic nucleoside phosphonates

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  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. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Interaction of phosphates of the acyclic nucleoside phosphonates with nucleoside diphosphate kinase from yeast and bovine liver

    Czech Academy of Sciences Publication Activity Database

    Horská, Květoslava; Votruba, Ivan; Holý, Antonín

    2006-01-01

    Roč. 71, č. 1 (2006), s. 35-43 ISSN 0010-0765 R&D Projects: GA AV ČR(CZ) IBS4055109 Institutional research plan: CEZ:AV0Z40550506 Keywords : enzymatic phosphorylation * acyclic nucleotide analogs * NTP analogues Subject RIV: CC - Organic Chemistry Impact factor: 0.881, year: 2006

  1. Evaluation of Novel Acyclic Nucleoside Phosphonates against Human and Animal Gammaherpesviruses Revealed an Altered Metabolism of Cyclic Prodrugs upon Epstein-Barr Virus Reactivation in P3HR-1 Cells

    Czech Academy of Sciences Publication Activity Database

    Coen, N.; Duraffour, S.; Naesens, L.; Krečmerová, Marcela; Van Den Oord, J.; Snoeck, R.; Andrei, G.

    2013-01-01

    Roč. 87, č. 22 (2013), s. 12422-12432 ISSN 0022-538X R&D Projects: GA MPO FR-TI4/625 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate * gammaherpesvirus * Epstein-Barr virus * Kaposi's sarcoma * HPMP-5-azaC * cidofovir Subject RIV: EE - Microbiology, Virology Impact factor: 4.648, year: 2013

  2. Synthesis and Properties of a Novel Type of Acyclic Nucleoside Phosphonates: 2-(Purin-9-yl)ethoxyphenylphosphonic Acids

    Czech Academy of Sciences Publication Activity Database

    Hocková, Dana; Dračínský, Martin; Holý, Antonín

    -, č. 15 (2010), s. 2885-2892 ISSN 1434-193X R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleotides * phosphonates * cross-coupling Subject RIV: CC - Organic Chemistry Impact factor: 3.206, year: 2010

  3. 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

  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. 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

  6. Acyclic nucleoside phosphonates: A key class of antiviral drugs

    Czech Academy of Sciences Publication Activity Database

    De Clercq, E.; Holý, Antonín

    2005-01-01

    Roč. 4, č. 13 (2005), 928-940 ISSN 1474-1776 Institutional research plan: CEZ:AV0Z4055905 Keywords : tenofovir * adefovir * cidofovir Subject RIV: CC - Organic Chemistry Impact factor: 18.775, year: 2005

  7. 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

  8. 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.

  9. C-H Phosphonation of Pyrrolopyrimidines: Synthesis of Substituted 7-and 9-Deazapurine-8-phosphonate Derivatives

    Czech Academy of Sciences Publication Activity Database

    Sabat, Nazarii; Poštová Slavětínská, Lenka; Klepetářová, Blanka; Hocek, Michal

    2016-01-01

    Roč. 81, č. 19 (2016), s. 9507-9514 ISSN 0022-3263 R&D Projects: GA ČR(CZ) GA16-00178S; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : cross - coupling reactions * acyclic nucleoside phosphonates * biological activity Subject RIV: CC - Organic Chemistry Impact factor: 4.849, year: 2016

  10. Microwave-assisted hydrolysis of phosphonate diesters: an efficient protocol for the preparation of phosphonic acids

    Czech Academy of Sciences Publication Activity Database

    Jansa, Petr; Baszczyňski, Ondřej; Procházková, Eliška; Dračínský, Martin; Janeba, Zlatko

    2012-01-01

    Roč. 14, č. 8 (2012), s. 2282-2288 ISSN 1463-9262 R&D Projects: GA MV VG20102015046 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * DNA virus * retrovirus infections * cidofovir * organic-synthesis Subject RIV: CC - Organic Chemistry Impact factor: 6.828, year: 2012

  11. 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

  12. Acyclic nucleoside phosphonates: a study on cytochrome P450 gene expression

    Czech Academy of Sciences Publication Activity Database

    Nekvindová, J.; Contreras, J. A.; Juvan, P.; Tacer, K. F.; Anzenbacher, P.; Zídek, Zdeněk; Zapletalová, M.; Rozman, D.; Anzenbacherová, E.

    2014-01-01

    Roč. 44, č. 8 (2014), s. 708-715 ISSN 0049-8254 Grant - others:GA MŠk(CZ) CZ.1.07/2.3.00/20.0019; GA MŠk(CZ) CZ.1.05/2.1.00/01.003 Institutional support: RVO:68378041 Keywords : induction * drug metabolism * antiviral Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.199, year: 2014

  13. Chiral analysis of acyclic nucleoside phosphonates-based anti-aids drugs by capillary electrophoresis

    Czech Academy of Sciences Publication Activity Database

    Kašička, Václav; Šolínová, Veronika; Sázelová, Petra; Mikysková, Hana; Jansa, Petr; Krečmerová, Marcela; Holý, Antonín

    2012-01-01

    Roč. 106, - (2012), s604-s604 ISSN 0009-2770. [EuCheMS Chemistry Congress /4./. 26.08.2012-30.08.2012, Prague] R&D Projects: GA MŠk 1M0508; GA ČR(CZ) GA203/08/1428 Institutional research plan: CEZ:AV0Z40550506 Keywords : analytical methods * electrophoresis * enentioselectivity Subject RIV: CC - Organic Chemistry

  14. Crystal Structures of Acyclic Nucleoside Phosphonates in Complex with Escherichia coli Hypoxanthine Phosphoribosyltransferase

    Czech Academy of Sciences Publication Activity Database

    Eng, W. S.; Hocková, Dana; Špaček, Petr; Baszczyňski, Ondřej; Janeba, Zlatko; Naesens, L.; Keough, D. T.; Guddat, L. W.

    2016-01-01

    Roč. 1, č. 19 (2016), s. 6267-6276 ISSN 2365-6549 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : enzyme inhibitors * nucleotide analogues * HPRT Subject RIV: CC - Organic Chemistry

  15. Novel acyclic nucleoside phosphonate analogues with potent anti-hepatitis B virus activities

    Czech Academy of Sciences Publication Activity Database

    Ying, C.; Holý, Antonín; Hocková, Dana; Havlas, Zdeněk; De Clercq, E.; Neyts, J.

    2005-01-01

    Roč. 49, č. 3 (2005), 1177-1180 ISSN 0066-4804 R&D Projects: GA AV ČR(CZ) IBS4055109 Grant - others:FWO(BE) G.0267.04 Institutional research plan: CEZ:AV0Z4055905 Keywords : antivirals * hepatitis B * ANP Subject RIV: CC - Organic Chemistry Impact factor: 4.379, year: 2005

  16. Macrophage activation by antiviral acyclic nucleoside phosphonates in dependence on priming immune stimuli

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Franková, Daniela; Holý, Antonín

    2000-01-01

    Roč. 22, č. 12 (2000), s. 1121-1129 ISSN 0192-0561 R&D Projects: GA ČR GA305/00/0048; GA ČR GV203/96/K001 Institutional research plan: CEZ:AV0Z5008914 Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.142, year: 2000

  17. Phytotoxicity of acyclic nucleoside phosphonates in Brassica pekinensis and Solanum lycopersicum

    Czech Academy of Sciences Publication Activity Database

    Špak, Josef; Janeba, Zlatko; Jansa, Petr; Baszczyňski, Ondřej; Pavingerová, Daniela; Špaková, Vlastimila

    2016-01-01

    Roč. 125, č. 2 (2016), s. 375-379 ISSN 0167-6857 Institutional support: RVO:60077344 ; RVO:61388963 Keywords : Chemotherapy * Virus eradication * Phytotoxicity Subject RIV: EE - Microbiology, Virology; CC - Organic Chemistry (UOCHB-X) Impact factor: 2.002, year: 2016

  18. Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases

    Czech Academy of Sciences Publication Activity Database

    Hocková, Dana; Janeba, Zlatko; Naesens, L.; Edstein, M. D.; Chavchich, M.; Keough, D. T.; Guddat, L. W.

    2015-01-01

    Roč. 23, č. 17 (2015), s. 5502-5510 ISSN 0968-0896 R&D Projects: GA ČR GAP207/11/0108 Institutional support: RVO:61388963 Keywords : nucleotide analogues * enzyme inhibitors * malaria * HG(X)PRT * ANP Subject RIV: CC - Organic Chemistry Impact factor: 2.923, year: 2015

  19. Acyclic Nucleoside Phosphonates Containing a Second Phosphonate Group Are Potent Inhibitors of 6-Oxopurine Phosphoribosyltransferases and Have Antimalarial Activity

    Czech Academy of Sciences Publication Activity Database

    Keough, D. T.; Špaček, Petr; Hocková, Dana; Tichý, Tomáš; Vrbková, S.; Slavětínská, Lenka; Janeba, Zlatko; Naesens, L.; Edstein, M. D.; Chavchich, M.; Wang, T. H.; de Jersey, J.; Guddat, L. W.

    2013-01-01

    Roč. 56, č. 6 (2013), s. 2513-2526 ISSN 0022-2623 R&D Projects: GA ČR GAP207/11/0108 Institutional support: RVO:61388963 Keywords : enzyme inhibitors * ANPs * malaria * bisphosphonates Subject RIV: CC - Organic Chemistry Impact factor: 5.480, year: 2013

  20. Synthesis and biological evaluation of acyclic nucleotide analogues with a furo[2,3-d]pyrimidin-2(3H)-one base

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko; Holý, Antonín; Pohl, Radek; Snoeck, R.; Andrei, G.; De Clercq, E.; Balzarini, J.

    2010-01-01

    Roč. 88, č. 7 (2010), s. 628-638 ISSN 0008-4042 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * Sonogashira reaction * intramolecular cyclization Subject RIV: CC - Organic Chemistry Impact factor: 1.374, year: 2010

  1. Alternative synthesis of 9-{3-[(diisopropoxyphosphoryl)-methoxy]-2-hydroxypropyl}adenine and its free phosphonates substituted at the C-8 position of purine base

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko; Masojídková, Milena; Holý, Antonín

    2010-01-01

    Roč. 75, č. 3 (2010), s. 371-381 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * HPMPA * nucleophilic substitution * intramolecular cyclization Subject RIV: CC - Organic Chemistry Impact factor: 0.853, year: 2010

  2. Prolinol-based nucleoside phosphonic acids: new isosteric conformationally flexible nucleotide analogues

    Czech Academy of Sciences Publication Activity Database

    Vaněk, Václav; Buděšínský, Miloš; Rinnová, Markéta; Rosenberg, Ivan

    2009-01-01

    Roč. 65, č. 4 (2009), s. 862-876 ISSN 0040-4020 R&D Projects: GA ČR GA203/05/0827; GA MŠk(CZ) LC06077; GA MŠk LC512; GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleotide analogues * phosphonates * prolinol derivatives * N- alkylation Subject RIV: CC - Organic Chemistry Impact factor: 3.219, year: 2009

  3. Antiviral activity of acyclic nucleoside phosphonates PMEA, (S)-HPMPC, PMEDAP and ribavirin against Cauliflower mosaic virus in Brassica pekinensis

    Czech Academy of Sciences Publication Activity Database

    Špak, Josef; Votruba, Ivan; Pavingerová, Daniela; Holý, Antonín; Špaková, Vlastimila; Petrzik, Karel

    2012-01-01

    Roč. 10, č. 1 (2012), s. 63-68 ISSN 0167-6857 R&D Projects: GA ČR GA522/09/0707 Institutional research plan: CEZ:AV0Z50510513; CEZ:AV0Z40550506 Keywords : Caulimovirus * Chemotherapy * Pararetrovirus * dsDNA Subject RIV: EE - Microbiology, Virology Impact factor: 3.633, year: 2012

  4. Synthesis and Evaluation of Asymmetric Acyclic Nucleoside Bisphosphonates as Inhibitors of Plasmodium falciparum and Human Hypoxanthine-Guanine-(Xanthine) Phosphoribosyltransferase

    Czech Academy of Sciences Publication Activity Database

    Špaček, Petr; Keough, D. T.; Chavchich, M.; Dračínský, Martin; Janeba, Zlatko; Naesens, L.; Edstein, M. D.; Guddat, L. W.; Hocková, Dana

    2017-01-01

    Roč. 60, č. 17 (2017), s. 7539-7554 ISSN 0022-2623 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : hypoxanthine-guanine phosphoribosyltransferase * 2nd phosphonate group * 6-oxopurine phosphoribosyltransferases Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 6.259, year: 2016

  5. Aza-acyclic Nucleoside Phosphonates Containing a Second Phosphonate Group As Inhibitors of the Human, Plasmodium falciparum and vivax 6-Oxopurine Phosphoribosyltransferases and Their Prodrugs As Antimalarial Agents

    Czech Academy of Sciences Publication Activity Database

    Keough, D. T.; Hocková, Dana; Janeba, Zlatko; Wang, T. H.; Naesens, L.; Edstein, M. D.; Chavchich, M.; Guddat, L. W.

    2015-01-01

    Roč. 58, č. 2 (2015), s. 827-846 ISSN 0022-2623 R&D Projects: GA ČR GAP207/11/0108 Institutional support: RVO:61388963 Keywords : enzyme inhibitors * ANPs * Plasmodium * malaria Subject RIV: CC - Organic Chemistry Impact factor: 5.589, year: 2015

  6. Novel nucleotide analogues bearing (1H-1,2,3-triazol-4-yl)phosphonic acid moiety as inhibitors of Plasmodium and human 6-oxopurine phosphoribosyltransferases

    Czech Academy of Sciences Publication Activity Database

    Lukáč, Miloš; Hocková, Dana; Keough, D. T.; Guddat, L. W.; Janeba, Zlatko

    2017-01-01

    Roč. 73, č. 6 (2017), s. 692-702 ISSN 0040-4020 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * 6-oxopurine * hypoxanthine-guanine-(xanthine) phosphoribosyltransferase * copper(I)-catalyzed azide-alkyne cycloaddition Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.651, year: 2016

  7. Nucleoside-O-Methyl-(H)-Phosphinates: Novel Monomers for the Synthesis of Methylphosphonate Oligonucleotides Using H-Phosphonate Chemistry.

    Science.gov (United States)

    Kostov, Ondřej; Páv, Ondřej; Rosenberg, Ivan

    2017-09-18

    This unit comprises the straightforward synthesis of protected 2'-deoxyribonucleoside-O-methyl-(H)-phosphinates in both 3'- and 5'-series. These compounds represent a new class of monomers compatible with the solid-phase synthesis of oligonucleotides using H-phosphonate chemistry and are suitable for the preparation of both 3'- and 5'-O-methylphosphonate oligonucleotides. The synthesis of 4-toluenesulfonyloxymethyl-(H)-phosphinic acid as a new reagent for the preparation of O-methyl-(H)-phosphinic acid derivatives is described. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  8. Inhibition of human thymidine phosphorylase by conformationally constrained pyrimidine nucleoside phosphonic acids and their "open-structure" isosteres

    Czech Academy of Sciences Publication Activity Database

    Kóšiová, Ivana; Šimák, Ondřej; Panova, Natalya; Buděšínský, Miloš; Petrová, Magdalena; Rejman, Dominik; Liboska, Radek; Páv, Ondřej; Rosenberg, Ivan

    2014-01-01

    Roč. 74, Mar 3 (2014), s. 145-168 ISSN 0223-5234 R&D Projects: GA ČR GA203/09/0820; GA ČR GA202/09/0193; GA ČR GA13-24880S; GA ČR GA13-26526S Institutional support: RVO:61388963 Keywords : phosphonate * conformationally constrained nucleotide analog * human thymidine phosphorylase * PBMC * bi-substrate-like inhibitor * Michael addition Subject RIV: CC - Organic Chemistry Impact factor: 3.447, year: 2014

  9. First Crystal Structures of Mycobacterium tuberculosis 6-Oxopurine Phosphoribosyltransferase: Complexes with GMP and Pyrophosphate and with Acyclic Nucleoside Phosphonates Whose Prodrugs Have Antituberculosis Activity

    Czech Academy of Sciences Publication Activity Database

    Eng, W. S.; Hocková, Dana; Špaček, Petr; Janeba, Zlatko; West, N. P.; Woods, K.; Naesens, L. M. J.; Keough, D. T.; Guddat, L. W.

    2015-01-01

    Roč. 58, č. 11 (2015), s. 4822-4838 ISSN 0022-2623 R&D Projects: GA ČR GAP207/11/0108; GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : enzyme inhibitors * nucleotide analogues * tuberculosis * crystal structures Subject RIV: CC - Organic Chemistry Impact factor: 5.589, year: 2015

  10. Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates

    Czech Academy of Sciences Publication Activity Database

    Mandíková, J.; Volková, M.; Pávek, P.; Česnek, Michal; Janeba, Zlatko; Kubíček, V.; Trejtnar, F.

    2013-01-01

    Roč. 311, č. 3 (2013), s. 135-146 ISSN 0300-483X Institutional support: RVO:61388963 Keywords : hOAT1 * hCNTs * MDR1 * BCRP * nephrotoxicity * transmembrane transport Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.745, year: 2013

  11. Synthesis of Novel N-Branched Acyclic Nucleoside Phosphonates As Potent and Selective Inhibitors of Human, Plasmodium falciparum and Plasmodium vivax 6-Oxopurine Phosphoribosyltransferases

    Czech Academy of Sciences Publication Activity Database

    Hocková, Dana; Keough, D. T.; Janeba, Zlatko; Wang, T.; de Jersey, J.; Guddat, L. W.

    2012-01-01

    Roč. 55, č. 13 (2012), s. 6209-6223 ISSN 0022-2623 R&D Projects: GA ČR GAP207/11/0108; GA MŠk 1M0508 Grant - others:NHMRC(AU) 569703; NHMRC(AU) 1030353 Institutional support: RVO:61388963 Keywords : enzyme inhibitors * aza-ANPs * malaria Subject RIV: CC - Organic Chemistry Impact factor: 5.614, year: 2012

  12. Acyclic models

    CERN Document Server

    Barr, Michael

    2002-01-01

    Acyclic models is a method heavily used to analyze and compare various homology and cohomology theories appearing in topology and algebra. This book is the first attempt to put together in a concise form this important technique and to include all the necessary background. It presents a brief introduction to category theory and homological algebra. The author then gives the background of the theory of differential modules and chain complexes over an abelian category to state the main acyclic models theorem, generalizing and systemizing the earlier material. This is then applied to various cohomology theories in algebra and topology. The volume could be used as a text for a course that combines homological algebra and algebraic topology. Required background includes a standard course in abstract algebra and some knowledge of topology. The volume contains many exercises. It is also suitable as a reference work for researchers.

  13. Outstanding effects on antithrombin activity of modified TBA diastereomers containing an optically pure acyclic nucleotide analogue.

    Science.gov (United States)

    Scuotto, M; Persico, M; Bucci, M; Vellecco, V; Borbone, N; Morelli, E; Oliviero, G; Novellino, E; Piccialli, G; Cirino, G; Varra, M; Fattorusso, C; Mayol, L

    2014-07-28

    Herein, we report optically pure modified acyclic nucleosides as ideal probes for aptamer modification. These new monomers offer unique advantages in exploring the role played in thrombin inhibition by a single residue modification at key positions of the TBA structure.

  14. 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.

  15. Chiral analysis of anti-acquired immunodeficiency syndrome drug, 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using beta-CD as chiral selector

    Czech Academy of Sciences Publication Activity Database

    Šolínová, Veronika; Kašička, Václav; Sázelová, Petra; Holý, Antonín

    2009-01-01

    Roč. 30, č. 12 (2009), s. 2245-2254 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/06/1044; GA ČR(CZ) GA203/08/1428; GA AV ČR 1QS400550501; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : antiviral drugs * capillary electrophoresis * enantioseparation Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.077, year: 2009

  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. 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

  18. 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

  19. Synthesis of acyclic nucleoside 5-o-carboranyl uracil derivative ...

    African Journals Online (AJOL)

    carboranyl uracil 7 as potentially antiviral agent and a suitable candidate for BNCT is described starting from 5,5- dihydroxymethyl-1,3-dioxane 1, an intermediate 2,2,2-triacetoxymethyl ethoxymethyl acetyl 2 was synthesized and coupled with ...

  20. Acyclicity in edge-colored graphs

    DEFF Research Database (Denmark)

    Gutin, Gregory; Jones, Mark; Sheng, Bin

    2017-01-01

    A walk W in edge-colored graphs is called properly colored (PC) if every pair of consecutive edges in W is of different color. We introduce and study five types of PC acyclicity in edge-colored graphs such that graphs of PC acyclicity of type i is a proper superset of graphs of acyclicity of type...

  1. On Acyclicity of Games with Cycles

    DEFF Research Database (Denmark)

    Andersson, Daniel; Gurvich, Vladimir; Hansen, Thomas Dueholm

    2009-01-01

    We study restricted improvement cycles (ri-cycles) in finite positional n-person games with perfect information modeled by directed graphs (digraphs) that may contain cycles. We obtain criteria of restricted improvement acyclicity (ri-acyclicity) in two cases: for n = 2 and for acyclic digraphs. We...

  2. Synthesis, structural studies and biological properties of new TBA analogues containing an acyclic nucleotide.

    Science.gov (United States)

    Coppola, Teresa; Varra, Michela; Oliviero, Giorgia; Galeone, Aldo; D'Isa, Giuliana; Mayol, Luciano; Morelli, Elena; Bucci, Maria-Rosaria; Vellecco, Valentina; Cirino, Giuseppe; Borbone, Nicola

    2008-09-01

    A new modified acyclic nucleoside, namely N(1)-(3-hydroxy-2-hydroxymethyl-2-methylpropyl)-thymidine, was synthesized and transformed into a building block useful for oligonucleotide (ON) automated synthesis. A series of modified thrombin binding aptamers (TBAs) in which the new acyclic nucleoside replaces, one at the time, the thymidine residues were then synthesized and characterized by UV, CD, MS, and (1)H NMR. The biological activity of the resulting TBAs was tested by Prothrombin Time assay (PT assay) and by purified fibrinogen clotting assay. From a structural point of view, nearly all the new TBA analogues show a similar behavior as the unmodified counterpart, being able to fold into a bimolecular or monomolecular quadruplex structure depending on the nature of monovalent cations (sodium or potassium) coordinated in the quadruplex core. From the comparison of structural and biological data, some important structure-activity relationships emerged, particularly when the modification involved the TT loops. In agreement with previous studies we found that the folding ability of TBA analogues is more affected by modifications involving positions 4 and 13, rather than positions 3 and 12. On the other hand, the highest anti-thrombin activities were detected for aptamers containing the modification at T13 or T12 positions, thus indicating that the effects produced by the introduction of the acyclic nucleoside on the biological activity are not tightly connected with structure stabilities. It is noteworthy that the modification at T7 produces an ON being more stable and active than the natural TBA.

  3. Synthesis of New Acadesine (AICA-riboside Analogues Having Acyclic d-Ribityl or 4-Hydroxybutyl Chains in Place of the Ribose

    Directory of Open Access Journals (Sweden)

    Gennaro Piccialli

    2013-08-01

    Full Text Available The antiviral activity of certain acyclic nucleosides drew our attention to the fact that the replacement of the furanose ring by an alkyl group bearing hydroxyl(s could be a useful structural modification to modulate the biological properties of those nucleosides. Herein, we report on the synthesis of some novel acadesine analogues, where the ribose moiety is mimicked by a d-ribityl or by a hydroxybutyl chain.

  4. Isosteric phosphonate pyrrolidine-based dinucleoside monophosphate analogues

    Czech Academy of Sciences Publication Activity Database

    Vaněk, Václav; Buděšínský, Miloš; Kavenová, Ivana; Rinnová, Markéta; Rosenberg, Ivan

    2003-01-01

    Roč. 22, 5/8 (2003), s. 1065-1067 ISSN 1525-7770. [International Roundtable Nucleosides, Nucleotides and Nucleic Acids /15./. Leuven, 10.09.2002-14.09.2002] R&D Projects: GA ČR GA203/01/1166; GA AV ČR IAA4055101 Institutional research plan: CEZ:AV0Z4055905 Keywords : pyrrolidine-based phosphonate nucleotides * ApA analogues * triplex Subject RIV: CC - Organic Chemistry Impact factor: 0.813, year: 2003

  5. Geminal hydroxy phosphonate derivatives of nucleosides: A novel class of nucleoside 5'-monophosphate analogues

    Czech Academy of Sciences Publication Activity Database

    Králíková, Šárka; Buděšínský, Miloš; Masojídková, Milena; Rosenberg, Ivan

    2000-01-01

    Roč. 41, č. 6 (2000), s. 955-958 ISSN 0040-4039 R&D Projects: GA MŠk LB98233 Grant - others:NIH(US) R03 TW00673-01 Institutional research plan: CEZ:AV0Z4055905 Subject RIV: CC - Organic Chemistry Impact factor: 2.558, year: 2000

  6. Synthesis and configurational analysis of phosphonate cavitands

    NARCIS (Netherlands)

    Jacopozzi, Paola; Dalcanale, Enrico; Spera, Silvia; Chrisstoffels, L.A.J.; Reinhoudt, David; Lippmann, Tino; Mann, Gerhard

    1998-01-01

    Synthesis, separation and configurational analysis of phosphonated and partially phosphonated cavitands derived from resorcinarenes are described. The configuration of all diastereomers has been elucidated by their 1H, 31P NMR spectra and 13C relaxation times. In all cases the course of the bridging

  7. Synthesis of novel castor oil phosphonates

    Science.gov (United States)

    Castor oil has served as a versatile hydroxy fatty acid (HFA); its principle component, ricinoleic acid, can be isolated from castor oil and has been modified extensively for a number of applications. Additionally, phosphonates and their corresponding phosphonic acids are a functional moiety that ha...

  8. 3000 Horsepower super conductive field acyclic motor

    International Nuclear Information System (INIS)

    Marshall, R.

    1983-01-01

    A 3000 hp acyclic motor was assembled and tested utilizing superconducting field coils. The magnet assembly is designed as a quadrupole magnet, utilizing a multifilamentary niobium titanium superconductor. Each magnet coil is 18 inches in diameter and 10 inches long, and operates at rated current of 200 amperes, providing 5.8 tesla in the bore of the coils in the motor configuration. The average winding current density is 10,600 A/cm 2 . The acyclic motor is of a drum-type design with liquid metal current collectors, and is designed to model full-scale machinery for ship propulsion applications. Laboratory test data verified the electrical and electromagnetic design to be within three percent of the calculated values

  9. Acyclicity in edge-colored graphs

    DEFF Research Database (Denmark)

    Gutin, Gregory; Jones, Mark; Sheng, Bin

    2017-01-01

    A walk W in edge-colored graphs is called properly colored (PC) if every pair of consecutive edges in W is of different color. We introduce and study five types of PC acyclicity in edge-colored graphs such that graphs of PC acyclicity of type i is a proper superset of graphs of acyclicity of type i......+1, i=1,2,3,4. The first three types are equivalent to the absence of PC cycles, PC closed trails, and PC closed walks, respectively. While graphs of types 1, 2 and 3 can be recognized in polynomial time, the problem of recognizing graphs of type 4 is, somewhat surprisingly, NP-hard even for 2-edge-colored...... graphs (i.e., when only two colors are used). The same problem with respect to type 5 is polynomial-time solvable for all edge-colored graphs. Using the five types, we investigate the border between intractability and tractability for the problems of finding the maximum number of internally vertex...

  10. 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...

  11. Rhodium(iii)-catalyzed ortho-olefination of aryl phosphonates.

    Science.gov (United States)

    Chary, Bathoju Chandra; Kim, Sunggak

    2013-09-25

    Rhodium(iii)-catalyzed C-H olefination of aryl phosphonic esters is reported for the first time. In this mild and efficient process, the phosphonic ester group is utilized successfully as a new directing group. In addition, mono-olefination for aryl phosphonates is observed using a phosphonic diamide directing group.

  12. On the stereochemistry of C3'-O-P-CH2-O-C4'' phosphonate internucleotide bond, a phosphate isostere

    Czech Academy of Sciences Publication Activity Database

    Točík, Zdeněk; Buděšínský, Miloš; Barvík Jr., I.; Rosenberg, Ivan

    -, č. 52 (2008), s. 427-428 ISSN 0261-3166. [Joint Symposium of the International Roundtable on Nucleosides, Nucleotides and Nucleic Acids /18./ and the International Symposium on Nucleic Acid Chemistry /35./. Kyoto, 08.09.2008-12.09.2008] R&D Projects: GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z40550506 Keywords : phosphonate oligonucleotide stereochemistry Subject RIV: CC - Organic Chemistry

  13. Impossibility of an acyclic relativistic electric motor

    Energy Technology Data Exchange (ETDEWEB)

    Spavieri, G [Universidad de Los Andes, Merida (Venezuela); Cavalleri, G [Milan Univ. (Italy). Ist. di Fisica; Spinelli, G [Padua Univ. (Italy). Ist. di Matematica Applicata

    1981-02-11

    The relativistic torque acting on a circuit carrying a current and having a uniform translatory motion in a constant and uniform electric field would seem to suggest the possibility of an acyclic relativistic electric motor. However, the net effect on the side parallel to the rotation axis is exactly balanced by the variation of the angular momentum (in the case of an insulating circuit transporting electric charges) or by the external moment due to the magnetic field (in the case of a conducting circuit) acting on the two sides perpendicular to the rotation axis.

  14. Methyl 4-toluenesulfonyloxymethylphosphonate, a new and versatile reagent for the convenient synthesis of phosphonate-containing compounds

    Czech Academy of Sciences Publication Activity Database

    Kóšiová, Ivana; Točík, Zdeněk; Buděšínský, Miloš; Šimák, Ondřej; Liboska, Radek; Rejman, Dominik; Pačes, Ondřej; Rosenberg, Ivan

    2009-01-01

    Roč. 50, č. 49 (2009), s. 6745-6747 ISSN 0040-4039 R&D Projects: GA ČR GA202/09/0193; GA ČR GA203/09/0820; GA MŠk(CZ) LC06061; GA MŠk(CZ) LC06077; GA AV ČR KAN200520801 Institutional research plan: CEZ:AV0Z40550506 Keywords : nucleoside phosphonates * phosphonylation * methyl 4-toluenesulfonyloxymethylphosphonate Subject RIV: CC - Organic Chemistry Impact factor: 2.660, year: 2009

  15. Copper-Catalyzed Synthesis of Mixed Alkyl Aryl Phosphonates

    NARCIS (Netherlands)

    Fañanás-Mastral, Martín; Feringa, Ben L

    2014-01-01

    Copper-catalysis allows the direct oxygenarylation of dialkyl phosphonates with diaryliodonium salts. This novel methodology proceeds with a wide range of phosphonates and phosphoramidates under mild conditions and gives straightforward access to valuable mixed alkyl aryl phosphonates in very good

  16. On Event Detection and Localization in Acyclic Flow Networks

    KAUST Repository

    Suresh, Mahima Agumbe; Stoleru, Radu; Zechman, Emily M.; Shihada, Basem

    2013-01-01

    Acyclic flow networks, present in many infrastructures of national importance (e.g., oil and gas and water distribution systems), have been attracting immense research interest. Existing solutions for detecting and locating attacks against

  17. Actinide phosphonate complexes in aqueous solutions

    International Nuclear Information System (INIS)

    Nash, K.L.

    1993-01-01

    Complexes formed by actinides with carboxylic acids, polycarboxylic acids, and aminopolycarboxylic acids play a central role in both the basic and process chemistry of the actinides. Recent studies of f-element complexes with phosphonic acid ligands indicate that new ligands incorporating doubly ionizable phosphonate groups (-PO 3 H 2 ) have many properties which are unique chemically, and promise more efficient separation processes for waste cleanup and environmental restoration. Simple diphosphonate ligands form much stronger complexes than isostructural carboxylates, often exhibiting higher solubility as well. In this manuscript recent studies of the thermodynamics and kinetics of f-element complexation by 1,1 and 1,2 diphosphonic acid ligands are described

  18. Synthesis of difluorinated compounds starting from phosphonates

    Czech Academy of Sciences Publication Activity Database

    Alexandrova, Anastasia; Beier, Petr

    2008-01-01

    Roč. 102, č. 11 (2008), s. 1023-1023 ISSN 0009-2770. [Pokroky v organické, bioorganické a farmaceutické chemii /43./. 14.11.2008-16.11.2008, Liblice] Institutional research plan: CEZ:AV0Z40550506 Keywords : phosphonates * nucleophilic addition Subject RIV: CC - Organic Chemistry

  19. Evaluation of nucleoside phosphonates and their analogs and prodrugs for inhibition of orthopoxvirus replication

    Czech Academy of Sciences Publication Activity Database

    Keith, K. A.; Hitchcock, M. J. M.; Lee, W. A.; Holý, Antonín; Kern, E. R.

    2003-01-01

    Roč. 47, č. 7 (2003), s. 2193-2198 ISSN 0066-4804 R&D Projects: GA AV ČR IBS4055109 Grant - others:Public Health Service(US) NO1-AI-85347 Institutional research plan: CEZ:AV0Z4055905 Keywords : adefovir * cidofovir * tenofovir Subject RIV: CC - Organic Chemistry Impact factor: 4.246, year: 2003

  20. Synthesis and Early Development of Hexadecyloxypropyl-cidofovir: An Oral Antipoxvirus Nucleoside Phosphonate

    Directory of Open Access Journals (Sweden)

    Karl Y. Hostetler

    2010-09-01

    Full Text Available Hexadecyloxypropyl-cidofovir (HDP-CDV is a novel ether lipid conjugate of (S-1-(3-hydroxy-2-phosphonoylmethoxypropyl-cytosine (CDV which exhibits a remarkable increase in antiviral activity against orthopoxviruses compared with CDV. In contrast to CDV, HDP-CDV is orally active and lacks the nephrotoxicity of CDV itself. Increased oral bioavailability and increased cellular uptake is facilitated by the lipid portion of the molecule which is responsible for the improved activity profile. The lipid portion of HDP-CDV is cleaved in the cell, releasing CDV which is converted to CDV diphosphate, the active metabolite. HDP-CDV is a highly effective agent against a variety of orthopoxvirus infections in animal models of disease including vaccinia, cowpox, rabbitpox and ectromelia. Its activity was recently demonstrated in a case of human disseminated vaccinia infection after it was added to a multiple drug regimen. In addition to the activity against orthopoxviruses, HDP-CDV (CMX001 is active against all double stranded DNA viruses including CMV, HSV-1, HSV-2, EBV, adenovirus, BK virus, orf, JC, and papilloma viruses, and is under clinical evaluation as a treatment for human infections with these agents.

  1. 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.

  2. Self-ordered Porous Alumina Fabricated via Phosphonic Acid Anodizing

    OpenAIRE

    Akiya, Shunta; Kikuchi, Tatsuya; Natsui, Shungo; Sakaguchi, Norihito; Suzuki, Ryosuke O.

    2016-01-01

    Self-ordered periodic porous alumina with an undiscovered cell diameter was fabricated via electrochemical anodizing in a new electrolyte, phosphonic acid (H3PO3). High-purity aluminum plates were anodized in phosphonic acid solution under various operating conditions of voltage, temperature, concentration, and anodizing time. Phosphonic acid anodizing at 150-180 V caused the self-ordering behavior of porous alumina, and an ideal honeycomb nanostructure measuring 370-440 nm in cell diameter w...

  3. 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

  4. Polynomial kernels for deletion to classes of acyclic digraphs

    NARCIS (Netherlands)

    Mnich, Matthias; van Leeuwen, E.J.

    2017-01-01

    We consider the problem to find a set X of vertices (or arcs) with |X| ≤ k in a given digraph G such that D = G − X is an acyclic digraph. In its generality, this is Directed Feedback Vertex Set (or Directed Feedback Arc Set); the existence of a polynomial kernel for these problems is a notorious

  5. Hydrophosphorylation of substituted alkynes by phosphonic acids

    International Nuclear Information System (INIS)

    Nifant'ev, E.F.; Solovetskaya, L.A.; Maslennikova, V.I.; Sergeev, N.M.

    1987-01-01

    Hydrophosphorylation of functionally substituted alkynes by phosphonic acids can be a convenient method for synthesis of functionally substituted mono- and diphosphine oxides. The ease of hydrophosphorylation is determined by the strength of the negative inductive effect of the substituents on the triple bond and the steric factor. The structure of the bis-adducts was confirmed by elementary analysis and the 31 P and 13 C NMR spectra. The 31 P NMR spectrum is an AB two-spin system. The values of the chemical shifts and spin-spin interaction constants 3 J/sub PP/ are in agreement with the data in the literature for similar compounds

  6. 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...

  7. 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.

  8. Room-Temperature Alternative to the Arbuzov Reaction: The Reductive Deoxygenation of Acyl Phosphonates

    OpenAIRE

    Kedrowski, Sean M. A.; Dougherty, Dennis A.

    2010-01-01

    The reductive deoxygenation of acyl phosphonates using a Wolff−Kishner-like sequence is described. This transformation allows direct access to alkyl phosphonates from acyl phosphonates at room temperature. The method can be combined with acyl phosphonate synthesis into a one pot, four-step procedure for the conversion of carboxylic acids into alkyl phosphonates. The methodology works well for a variety of aliphatic acids and shows a functional group tolerance similar to that of other hydrazon...

  9. Alkyl phosphonic acids and sulfonic acids in the Murchison meteorite

    Science.gov (United States)

    Cooper, George W.; Onwo, Wilfred M.; Cronin, John R.

    1992-01-01

    Homologous series of alkyl phosphonic acids and alkyl sulfonic acids, along with inorganic orthophosphate and sulfate, are identified in water extracts of the Murchison meteorite after conversion to their t-butyl dimethylsilyl derivatives. The methyl, ethyl, propyl, and butyl compounds are observed in both series. Five of the eight possible alkyl phosphonic acids and seven of the eight possible alkyl sulfonic acids through C4 are identified. Abundances decrease with increasing carbon number as observed of other homologous series indigenous to Murchison. Concentrations range downward from approximately 380 nmol/gram in the alkyl sulfonic acid series, and from 9 nmol/gram in the alkyl phosphonic acid series.

  10. 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.

  11. Synthesis of analogues of acyclic nucleoside diphosphates containing a (phosphonomethyl)phosphanyl moiety and studies of their phosphorylation

    Czech Academy of Sciences Publication Activity Database

    Doláková, Petra; Dračínský, Martin; Fanfrlík, Jindřich; Holý, Antonín

    -, č. 7 (2009), s. 1082-1092 ISSN 1434-193X R&D Projects: GA AV ČR 1QS400550501 Grant - others:NIH(US) 1UC1AI062540-01 Institutional research plan: CEZ:AV0Z40550506 Keywords : antiviral agents * nucleotides * phosphorylation * dUTPase Subject RIV: CC - Organic Chemistry Impact factor: 3.096, year: 2009

  12. Synthesis of tritium labelled phosphonate analogues of sphinganine-1-phosphate

    International Nuclear Information System (INIS)

    Schick, Andreas; Schwarzmann, Guenter; Kolter, Thomas; Sandhoff, Konrad

    1997-01-01

    Tritiated phosphonate analogues 9 and 10 are prepared as analogues of sphinganine-1-phosphate 4. The key step in this synthesis is the catalytic tritiation of the triple bond in reduction of the protected diethyl-3-(S)-tert.-butoxycarbonylamino -4-hydroxy-5-tridecinyl-1-phosphonate by means of sodium boro[ 3 H]hydride as tritium source. These compounds are synthesized to study their metabolic stability and to evaluate their biological properties. (author)

  13. Recent advances in H-phosphonate chemistry. Part 1. H-phosphonate esters: synthesis and basic reactions.

    Science.gov (United States)

    Sobkowski, Michal; Kraszewski, Adam; Stawinski, Jacek

    2015-01-01

    This review covers recent progress in the preparation of H-phosphonate mono- and diesters, basic studies on mechanistic and stereochemical aspects of this class of phosphorus compounds, and their fundamental chemistry in terms of transformation of P-H bonds into P-heteroatom bonds. Selected recent applications of H-phosphonate derivatives in basic organic phosphorus chemistry and in the synthesis of biologically important phosphorus compounds are also discussed.

  14. 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.

  15. 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.

  16. On Event Detection and Localization in Acyclic Flow Networks

    KAUST Repository

    Suresh, Mahima Agumbe

    2013-05-01

    Acyclic flow networks, present in many infrastructures of national importance (e.g., oil and gas and water distribution systems), have been attracting immense research interest. Existing solutions for detecting and locating attacks against these infrastructures have been proven costly and imprecise, particularly when dealing with large-scale distribution systems. In this article, to the best of our knowledge, for the first time, we investigate how mobile sensor networks can be used for optimal event detection and localization in acyclic flow networks. We propose the idea of using sensors that move along the edges of the network and detect events (i.e., attacks). To localize the events, sensors detect proximity to beacons, which are devices with known placement in the network. We formulate the problem of minimizing the cost of monitoring infrastructure (i.e., minimizing the number of sensors and beacons deployed) in a predetermined zone of interest, while ensuring a degree of coverage by sensors and a required accuracy in locating events using beacons. We propose algorithms for solving the aforementioned problem and demonstrate their effectiveness with results obtained from a realistic flow network simulator.

  17. Towards Optimal Event Detection and Localization in Acyclic Flow Networks

    KAUST Repository

    Agumbe Suresh, Mahima

    2012-01-03

    Acyclic flow networks, present in many infrastructures of national importance (e.g., oil & gas and water distribution systems), have been attracting immense research interest. Existing solutions for detecting and locating attacks against these infrastructures, have been proven costly and imprecise, especially when dealing with large scale distribution systems. In this paper, to the best of our knowledge for the first time, we investigate how mobile sensor networks can be used for optimal event detection and localization in acyclic flow networks. Sensor nodes move along the edges of the network and detect events (i.e., attacks) and proximity to beacon nodes with known placement in the network. We formulate the problem of minimizing the cost of monitoring infrastructure (i.e., minimizing the number of sensor and beacon nodes deployed), while ensuring a degree of sensing coverage in a zone of interest and a required accuracy in locating events. We propose algorithms for solving these problems and demonstrate their effectiveness with results obtained from a high fidelity simulator.

  18. Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

    Czech Academy of Sciences Publication Activity Database

    Blindauer, C. A.; Sigel, A.; Operschall, B. P.; Holý, Antonín; Sigel, H.

    2018-01-01

    Roč. 472, Mar 1 (2018), s. 283-294 ISSN 0020-1693 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * antivirals * chelates * isomeric equilibria * metal ion complexes * nucleotide analogues Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.002, year: 2016

  19. Synthesis and biological properties of prodrugs of (S)-3-(adenin-9-yl)-2-(phosphonomethoxy)propanoic acid

    Czech Academy of Sciences Publication Activity Database

    Kaiser, Martin Maxmilian; Poštová Slavětínská, Lenka; Dračínský, Martin; Lee, Y. J.; Tian, Y.; Janeba, Zlatko

    2016-01-01

    Roč. 108, Jan 27 (2016), s. 374-380 ISSN 0223-5234 R&D Projects: GA MV VG20102015046 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * (S)-CPMEA * antiviral * HCV * prodrugs Subject RIV: CC - Organic Chemistry Impact factor: 4.519, year: 2016

  20. Permeation enhancer dedocyl 6-(dimethylamino)hexanoate increases transdermal and topical delivery of adefovir: Influence of pH, ion-pairing and skin species

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Lorencová, K.; Novotný, J.; Holý, Antonín; Hrabálek, A.

    2008-01-01

    Roč. 70, č. 3 (2008), s. 901-907 ISSN 0939-6411 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : adefovir * acyclic nucleoside phosphonates * antiviral * transdermal drug delivery * permeation enhancer Subject RIV: CC - Organic Chemistry Impact factor: 3.344, year: 2008

  1. Solution properties of metal ion complexes formed with the antiviral and cytostatic nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]-2-amino-6-dimethylaminopurine (PME2A6DMAP)

    Czech Academy of Sciences Publication Activity Database

    Gómez-Coca, R. B.; Sigel, A.; Operschall, B. P.; Holý, Antonín; Sigel, H.

    2014-01-01

    Roč. 92, č. 8 (2014), s. 771-780 ISSN 0008-4042 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * antivirals * intramolecular equilibria * metal-ion complexes * nucleotide analogues * stability constants Subject RIV: CC - Organic Chemistry Impact factor: 1.061, year: 2014

  2. Oligomeric state of hypoxanthine-guanine phosphoribosyltransferase from Mycobacterium tuberculosis

    Czech Academy of Sciences Publication Activity Database

    Eng, W. S.; Keough, D. T.; Hocková, Dana; Winzor, D. J.; Guddat, L. W.

    2017-01-01

    Roč. 135, Apr (2017), s. 6-14 ISSN 0300-9084 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : enzyme inhibitors * acyclic nucleoside phosphonates * 6-oxopurine phosphoribosyltransferase Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.112, year: 2016

  3. Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Diblíková, D.; Kopečná, M.; Školová, B.; Krečmerová, Marcela; Roh, J.; Hrabálek, A.; Vávrová, K.

    2014-01-01

    Roč. 31, č. 4 (2014), s. 1071-1081 ISSN 0724-8741 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate antivirals * lysolipid prodrug * penetration enhancer * skin absorption * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.420, year: 2014

  4. 9-[2-(R)-(Phosphonomethoxy)propyl]-2,6-diaminopurine (R)-PMPDAP and its prodrugs: Optimized preparation, including identification of by-products formed, and antiviral evaluation in vitro

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Jansa, Petr; Dračínský, Martin; Sázelová, Petra; Kašička, Václav; Neyts, J.; Auwerx, J.; Kiss, E.; Goris, N.; Stepan, G.; Janeba, Zlatko

    2013-01-01

    Roč. 21, č. 5 (2013), s. 1199-1208 ISSN 0968-0896 R&D Projects: GA MŠk(CZ) ME10040 Institutional support: RVO:61388963 Keywords : PMPDAP * Acyclic nucleoside phosphonates * (Phosphonomethoxy)propyl * purine * antivirals * HIV Subject RIV: CC - Organic Chemistry Impact factor: 2.951, year: 2013

  5. Role acyklických nukleosidfosfonátů jako potenciálních antimalarik

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko; Hocková, Dana

    2014-01-01

    Roč. 108, č. 4 (2014), s. 335-343 ISSN 0009-2770 R&D Projects: GA ČR GAP207/11/0108 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * prodrugs * antivirals * antimalarials Subject RIV: CC - Organic Chemistry Impact factor: 0.272, year: 2014

  6. Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells

    Czech Academy of Sciences Publication Activity Database

    Mertlíková-Kaiserová, Helena; Votruba, Ivan; Matoušová, Marika; Holý, Antonín; Hájek, Miroslav

    2010-01-01

    Roč. 30, č. 7 (2010), s. 2791-2798 ISSN 0250-7005 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonate * programmed cell death * CCRF-CEM cells * cell cycle Subject RIV: CC - Organic Chemistry Impact factor: 1.656, year: 2010

  7. Synthesis of 9-phosphonoalkyl and 9-phosphonoalkoxyalkyl purines: Evaluation of their ability to act as inhibitors of Plasmodium falciparum, Plasmodium vivax and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases

    Czech Academy of Sciences Publication Activity Database

    Česnek, Michal; Hocková, Dana; Holý, Antonín; Dračínský, Martin; Baszczyňski, Ondřej; de Jersey, J.; Keough, D. T.; Guddat, L. W.

    2012-01-01

    Roč. 20, č. 2 (2012), s. 1076-1089 ISSN 0968-0896 R&D Projects: GA MŠk 1M0508; GA ČR GAP207/11/0108 Institutional research plan: CEZ:AV0Z40550506 Keywords : Plasmodium * malaria * acyclic nucleoside phosphonates Subject RIV: CC - Organic Chemistry Impact factor: 2.903, year: 2012

  8. Extent of Intramolecular p-Stacks in Aqueous Solution in Mixed-Ligand Copper(II) Complexes Formed by Heteroaromatic Amines and Several 2-Aminopurine Derivatives of the Antivirally Active Nucleotide Analog 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA)

    Czech Academy of Sciences Publication Activity Database

    Gómez-Coca, R. B.; Blindauer, C. A.; Sigel, A.; Operschall, B. P.; Holý, Antonín; Sigel, H.

    2012-01-01

    Roč. 9, č. 9 (2012), s. 2008-2034 ISSN 1612-1872 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : copper complexes * nucleotides * acyclic nucleoside phosphonates * ANPs * antiviral activity Subject RIV: CE - Biochemistry Impact factor: 1.808, year: 2012

  9. Mutations Conferring Resistance to Viral DNA Polymerase Inhibitors in Camelpox Virus Give Different Drug-Susceptibility Profiles in Vaccinia Virus

    Czech Academy of Sciences Publication Activity Database

    Duraffour, S.; Andrei, G.; Topalis, D.; Krečmerová, Marcela; Crance, J. M.; Garin, D.; Snoeck, R.

    2012-01-01

    Roč. 86, č. 13 (2012), s. 7310-7325 ISSN 0022-538X Institutional support: RVO:61388963 Keywords : camelpox virus * CMLV * vaccinia virus VACV * acyclic nucleoside phosphonates * HPMPDAP * cidofovir * drug resistance Subject RIV: CC - Organic Chemistry Impact factor: 5.076, year: 2012

  10. 6-Oxopurine Phosphoribosyltransferase: A Target for the Development of Antimalarial Drugs

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

    Roč. 11, č. 16 (2011), s. 2085-2102 ISSN 1568-0266 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : Malaria * acyclic nucleoside phosphonates * hypoxanthine * guanine phosphoribosyl transferase Subject RIV: CC - Organic Chemistry Impact factor: 4.174, year: 2011

  11. 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

  12. Reactions of acetylenes with hypophosphorous and phosphonous acids

    International Nuclear Information System (INIS)

    Nifant'ev, E.E.; Solovetskaya, L.A.; Maslennikova, V.I.; Magdeeva, R.K.; Sergeev, N.M.

    1986-01-01

    Alkenylphosphonous, alkenylphosphinic, and alkylenebisphosphinic acids were prepared for the first time. The course of the hydrophosphorylation of 1-alkynes depends on the form of the reagent used. The homolytic hydrophosphorylation of acetylenes with hypophosphorous acid proceeds mainly with the participation of one molecule of the acid. The addition of phosphonous acids to acetylenic hydrocarbons leads to both mono- and di-phosphorylated adducts. The nature of the phosphonous acid taken has a substantial influence on the readiness with which the alkylenebisphosphinic acids are formed. Study of the stereoselectivity of the reactions showed that in the case of the monoaddition of hypophosphorous and phosphonous acids to acetylenes mixtures of cis and trans isomeric products are always formed. Phosphorous 31 and carbon 13 NMR spectra are analyzed

  13. Extraction studies of actinides by diamylbutyl phosphonate

    International Nuclear Information System (INIS)

    Brahmananda Rao, C.V.S.; Jayalakshmi, S.; Subramaniam, S.; Sabharwal, K.N.; Sivaraman, N.; Vasudeva Rao, P.R.

    2014-01-01

    The extraction ability of a monodentate organophosphorus extractant depends on the basicity of the phosphoryl oxygen atom and the nature of the substituents attached to the phosphorus atom. The basicity on the phosphoryl oxygen in the neutral organophosphorus extractant series increases in the order, phosphates 1 H, 13 C and 31 P NMR spectra. Extraction of U(VI) by 1.1 M DABP/n-dodecane as a function of nitric acid was studied using 233 U tracer. Th(IV) extraction behaviour as a function of nitric acid was studied using Arsenazo-III as chromogenic agent. 5 mL of the 1.1 M DABP solution in the diluent (n-dodecane) was equilibrated with 5mL of saturated thorium nitrate in an equilibration tube using a magnetic stirring bar. The organic and aqueous phases were analysed by complexometry using DTPA as titrant and xylenol orange as indicator. The LOC values were determined as a function of nitric acid concentration. The extraction of U(VI) and Th(IV) by 1.1M DABP along with TBP in n-dodecane at 303 K as a function of equilibrium nitric acid concentration are shown. The DABP shows higher distribution ratios for U(VI) and Th(IV) in the entire range of nitric acid concentrations studied compared to TBP. The steep rise in the distribution ratio is attributed to the higher basicity of phosphoryl group in phosphonates compared to the less basic nature of phosphates. The third phase formation of thorium as function of nitric acid concentration with 1.1 M DABP at 303 K are given. The LOC values for DABP system were higher throughout the nitric acid concentration compared to the TBP system. (author)

  14. Detecting Elusive Intermediates in Carbohydrate Conversion: A Dynamic Ensemble of Acyclic Glucose-Catalyst Complexes

    DEFF Research Database (Denmark)

    Meier, Sebastian; Karlsson, Magnus; Jensen, Pernille Rose

    2017-01-01

    within few seconds prior to reaching a steady state. Exchange between the acyclic intermediates increases at conditions that favor epimerization. Species accounting for less than 0.05% of total glucose can be monitored with sub-second time resolution to allow kinetic analysis of intermediate formation...... and catalytic conversion. Epimerization occurs 2-3 orders of magnitude-fold faster than the binding of acyclic glucose to the catalyst at near-optimum reaction conditions. The current study brings insight in to the nature of acyclic intermediate-catalyst complexes of very low population and into experimental...... strategies for characterizing very minor intermediates in carbohydrate conversion to value-added compounds....

  15. An Algorithm for Determining Minimal Reduced—Coverings of Acyclic Database Schemes

    Institute of Scientific and Technical Information of China (English)

    刘铁英; 叶新铭

    1996-01-01

    This paper reports an algoritm(DTV)for deermining the minimal reducedcovering of an acyclic database scheme over a specified subset of attributes.The output of this algotithm contains not only minimum number of attributes but also minimum number of partial relation schemes.The algorithm has complexity O(|N|·|E|2),where|N| is the number of attributes and |E|the number of relation schemes.It is also proved that for Berge,γ or β acyclic database schemes,the output of algorithm DTV maintains the acyclicity correspondence.

  16. Thermodynamics and kinetics of thermal decomposition of dibutylalkyl and dipentylalkyl phosphonate-nitric acid systems

    International Nuclear Information System (INIS)

    Chandran, K.; Brahmananda, C.V.S.; Anthonysamy, S.; Srinivasan, T.G.; Ganesan, V.

    2013-01-01

    Tributyl phosphate (TBP) is used in the reprocessing industry for the separation of uranium and plutonium from the spent nuclear fuels by PUREX process. A variety of dialkylalky/phosphonates were synthesised and their extraction behaviour on actinides was studied in this laboratory. The superior extraction characteristics of phosphonates make them useful for several metal recovery applications in the nuclear fuel cycle. However, higher solubility of phosphonates in aqueous phase as compared to TBP, introduces higher chances of the formation of thermally active 'red oil' like substances during the evaporation of aqueous streams. Thermal stability of neat and nitric acid solvated homologues of four dibutylalkyl phosphonates namely, dibutylpropyl phosphonate (DBPrP), dibutylbutyl phosphonate (DBBP), dibutylpentyl phosphonate (DBPP), dibutylhexyl phosphonate (DBHeP), and two dipentylalkyl phosphonates viz. dipentylbutyl phosphonate (DPBP), dipentylhexyl phosphonate (DPHeP) were studied. Experiments were conducted using an adiabatic calorimeter in heat-wait-search mode. Various stoichiometry of nitric acid-solvated DBalP and DPalP were prepared by equilibrating the respective organic with 4-15.6 M nitric acid followed by separation. Neat DBalP and DPalP are stable up to the temperature of ∼ 555 K while their acid-solvates decomposed in the temperature range 380-403 K. The results also indicated that the presence of nitric acid accelerated the decomposition of phosphonates. Decomposition of these acid solvated phosphonates is found to be exothermic and follows first order kinetics. The onset temperature, adiabatic temperature rise, pressure rise, decomposition enthalpy and activation energy were found to strongly depend on the nitric acid content of the acid-solvates. The studies also indicate that dibutylalkyl and dipentylalkyl phosphonates are also prone to form 'red oil' like substances under extreme conditions and can lead to run-away reactions

  17. Formation of phosphonates and pyrophosphates in the reactions of ...

    Indian Academy of Sciences (India)

    Bu-4-Me-C6H2O)2P(O)]2O (8) could be isolated, although the reaction mixture showed several other compounds in the phosphorus NMR. A possible pathway for the formation of phosphonate salts is proposed. The X-ray crystal structures of 4, ...

  18. Structure and properties of polyaniline interacting with H-phosphonates

    Czech Academy of Sciences Publication Activity Database

    Bláha, Michal; Trchová, Miroslava; Bober, Patrycja; Morávková, Zuzana; Zujovic, Z. D.; Filippov, Sergey K.; Prokeš, J.; Pilař, Jan; Stejskal, Jaroslav

    2017-01-01

    Roč. 232, October (2017), s. 79-86 ISSN 0379-6779 R&D Projects: GA ČR(CZ) GA17-04109S Institutional support: RVO:61389013 Keywords : conducting polymers * polyaniline * H-phosphonate Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 2.435, year: 2016

  19. New copper aryl phosphonates with auxiliary nitrogen ligands

    Czech Academy of Sciences Publication Activity Database

    Zima, Vítězslav; Svoboda, Jan; Yang, Y.-Ch.; Wang, S.-L.

    2012-01-01

    Roč. 14, č. 10 (2012), s. 3469-3477 ISSN 1466-8033 R&D Projects: GA ČR GA203/08/0208 Institutional research plan: CEZ:AV0Z40500505 Keywords : copper * phosphonates * structure Subject RIV: CA - Inorganic Chemistry Impact factor: 3.879, year: 2012

  20. Styrene-divinylbenzene copolymer grafted with phosphonic acid dialkylesters

    Directory of Open Access Journals (Sweden)

    SMARANDA ILIESCU

    2004-12-01

    Full Text Available The functionalization of a crosslinked chloromethylated polystyrene 8% divinylbenzene copolymer with phosphonic ester groups is detailed. The reacton conditions were studied in order to determine the optimal conditions for obtaining only diesters. A statistical method for the calculation of the fraction of repetive units for the inited and final resin is proposed.

  1. Highly selective Ba2+ separations with acyclic, lipophilic di-[N-(X)sulfonyl carbamoyl] polyethers.

    Science.gov (United States)

    Elshani, Sadik; Chun, Sangki; Amiri-Eliasi, Bijan; Bartsch, Richard A

    2005-01-14

    New lipophilic acyclic polyethers with two N-(X)sulfonyl carbamoyl groups of "tunable" acidity exhibit remarkable selectivity for Ba2+ over other alkaline earth metal ions in competitive solvent extraction and transport across polymer inclusion membranes.

  2. Comparison of construction algorithms for minimal, acyclic, deterministic, finite-state automata from sets of strings

    NARCIS (Netherlands)

    Daciuk, J; Champarnaud, JM; Maurel, D

    2003-01-01

    This paper compares various methods for constructing minimal, deterministic, acyclic, finite-state automata (recognizers) from sets of words. Incremental, semi-incremental, and non-incremental methods have been implemented and evaluated.

  3. Learning directed acyclic graphs from large-scale genomics data.

    Science.gov (United States)

    Nikolay, Fabio; Pesavento, Marius; Kritikos, George; Typas, Nassos

    2017-09-20

    In this paper, we consider the problem of learning the genetic interaction map, i.e., the topology of a directed acyclic graph (DAG) of genetic interactions from noisy double-knockout (DK) data. Based on a set of well-established biological interaction models, we detect and classify the interactions between genes. We propose a novel linear integer optimization program called the Genetic-Interactions-Detector (GENIE) to identify the complex biological dependencies among genes and to compute the DAG topology that matches the DK measurements best. Furthermore, we extend the GENIE program by incorporating genetic interaction profile (GI-profile) data to further enhance the detection performance. In addition, we propose a sequential scalability technique for large sets of genes under study, in order to provide statistically significant results for real measurement data. Finally, we show via numeric simulations that the GENIE program and the GI-profile data extended GENIE (GI-GENIE) program clearly outperform the conventional techniques and present real data results for our proposed sequential scalability technique.

  4. 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 ...

  5. Extraction of uranium from aqueous solution by phosphonic acid-imbedded polyurethane foam

    International Nuclear Information System (INIS)

    Katragadda, S.; Gesser, H.D.; Chow, A.

    1997-01-01

    Phenylphosphonic acid was imbedded into the matrix of the polyurethane foam during the fabrication process of the polymer. The extraction of uranium by phosphonic acid-imbedded polyurethane foam and blank polyurethane (i.e., foam without phosphonic acid functional groups) was investigated. Phosphonic acid-imbedded foam showed superior extractability of uranium from solutions with pH = 7.0 ± 1.5 over a wide range of temperatures. (author)

  6. Performance and Compatibility of Phosphonate-Based Superplasticizers for Concrete

    Directory of Open Access Journals (Sweden)

    Luigi Coppola

    2017-07-01

    Full Text Available The paper deals with the effectiveness of an innovative phosphonate-based superplasticizer (PNH for ready mixed concrete. Concrete specimens were manufactured by considering a constant initial workability, equal to 220 mm slump at the end of the mixing procedure. Workability was measured at 0, 30, and 60 min to evaluate the workability retention performances of the innovative superplasticizer. Compressive tests at 1, 7, and 28 days were carried out to evaluate the influence of the phosphonate-based superplasticizer on concrete setting and hardening. The concrete mixes were designed by considering 13 different cements to assess the superplasticizer-cement compatibility. The PNH-based admixture showed a better performance in terms of water reduction and workability retention with respect to napthalenesulphonate based admixtures (NSF; however, a higher dosage of PNH with respect to polycarboxylate ethers (PCEs was needed to get the same initial fluidity.

  7. Phosphonate-hydroxyapatite hybrid compounds prepared by hydrothermal method

    Energy Technology Data Exchange (ETDEWEB)

    Agougui, H.; Aissa, A. [Laboratoire de Physico-Chimie des Materiaux, Faculte des sciences de Monastir, 5019 Monastir (Tunisia); Maggi, S. [CNR-IC Istituto di Cristallografia, via Amendola 122/O, 70126 Bari (Italy); Debbabi, M., E-mail: m.debbabi@yahoo.fr [Laboratoire de Physico-Chimie des Materiaux, Faculte des sciences de Monastir, 5019 Monastir (Tunisia)

    2010-12-15

    Calcium hydroxyapatite (CaHAp) was prepared in the presence of two alkylphosphonates, the tert-butyl phosphonic acid TBPOH and the 2-carboxyletylphosphonic acid 2-CEPA, by hydrothermal method at 120 deg. C for 15 h. The modification of hydroxyapatite by grafting organic moieties is confirmed by IR and NMR MAS ({sup 1}H and {sup 31}P) spectroscopy and chemical analysis. X-ray powder diffraction patterns show that the incorporation of organic moieties induces a significant loss of the material crystallinity and a clear increase of the unit cell lattice parameter a as function of 2-CEPA grafting rate. The specific surface area (SSA) increases with increasing phosphonate amount especially for 2-CEPA. All techniques show the lower reactivity of TBPOH due to the steric effects of tert-butyl, whereas the 2-CEPA with a linear chain and double acidic functions is more reactive and can replace the OH{sup -} groups of the apatitic structure.

  8. Phosphonate-hydroxyapatite hybrid compounds prepared by hydrothermal method

    International Nuclear Information System (INIS)

    Agougui, H.; Aissa, A.; Maggi, S.; Debbabi, M.

    2010-01-01

    Calcium hydroxyapatite (CaHAp) was prepared in the presence of two alkylphosphonates, the tert-butyl phosphonic acid TBPOH and the 2-carboxyletylphosphonic acid 2-CEPA, by hydrothermal method at 120 deg. C for 15 h. The modification of hydroxyapatite by grafting organic moieties is confirmed by IR and NMR MAS ( 1 H and 31 P) spectroscopy and chemical analysis. X-ray powder diffraction patterns show that the incorporation of organic moieties induces a significant loss of the material crystallinity and a clear increase of the unit cell lattice parameter a as function of 2-CEPA grafting rate. The specific surface area (SSA) increases with increasing phosphonate amount especially for 2-CEPA. All techniques show the lower reactivity of TBPOH due to the steric effects of tert-butyl, whereas the 2-CEPA with a linear chain and double acidic functions is more reactive and can replace the OH - groups of the apatitic structure.

  9. Novel polymeric phosphonate scale inhibitors for improved squeeze treatment lifetimes

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, G.E.; Poynton, N.; McLaughlin, K.; Clark, D.R.

    1996-12-31

    New patented chemistry has provided an exciting discovery which may be used to reduce costs in scale squeeze applications. Phosphomethylated polyamines (PMPAs) have been found to possess outstanding adsorption-desorption properties which generate long squeeze lifetimes. This paper describes the core-flood tests and modelling work, which highlight these properties, plus additional scale inhibition performance studies to demonstrate the all-round capabilities of this chemistry for squeeze treatments. An example of a PMPA is used to show the extremely viable adsorption and desorption isotherms. These illustrate the efficient way in which the desorption occurs to minimise the chemical in the returns with a benefit of reduced chemical content in the discharge. The PMPA also demonstrates that both polymer and phosphonate properties can be embraced in a single product (e.g. dual scale control mechanisms) confirming that this chemistry is a true polymeric phosphonate. 13 refs., 12 figs., 1 tab.

  10. Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

    Science.gov (United States)

    2016-01-01

    Summary Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry. As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic compounds bearing a phosphonate group on the ring is given. PMID:27559377

  11. 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.

  12. Novel open-framework architectures in lanthanide phosphonates

    Science.gov (United States)

    Groves, John A.; Stephens, Nicholas F.; Wright, Paul A.; Lightfoot, Philip

    2006-03-01

    Two novel three-dimensional lanthanide coordination polymers have been prepared hydrothermally with the phosphonic acid N,N-piperazine bis(methylenephosphonic acid), H 2O 3PCH 2N(C 2H 4) 2NCH 2PO 3H 2 ( LH 4). The structures of Gd 2( LH 2) 3ṡ3H 2O (I) and Nd 2( LH 2) 3ṡ9H 2O (II) have been characterised by single crystal X-ray techniques. One-dimensional 'lanthanide-phosphate' chains are a key feature in both structures, although there are major structural differences between the chains, with (I) displaying octahedral GdO 6 coordination and (II) showing eight-coordinate NdO 8 polyhedra. In each case, three-dimensional connectivity is completed by coordination of the phosphonate group resulting in open framework structures encapsulating loosely bound water molecules. Isostructural Y 3+ and Yb 3+ analogues of (I) have been prepared, suggesting that cation size is a key factor in controlling the differing reaction products. In the case of Y 2( LH 2) 3ṡ5H 2O, isostructural to (I), it is shown that the extra-framework water molecules may be removed reversibly without framework collapse. Structural relationships to other known lanthanide phosphonates are discussed.

  13. Phosphonate biosynthesis and catabolism: a treasure trove of unusual enzymology.

    Science.gov (United States)

    Peck, Spencer C; van der Donk, Wilfred A

    2013-08-01

    Natural product biosynthesis has proven a fertile ground for the discovery of novel chemistry. Herein we review the progress made in elucidating the biosynthetic pathways of phosphonate and phosphinate natural products such as the antibacterial compounds dehydrophos and fosfomycin, the herbicidal phosphinothricin-containing peptides, and the antimalarial compound FR-900098. In each case, investigation of the pathway has yielded unusual, and often unprecedented, biochemistry. Likewise, recent investigations have uncovered novel ways to cleave the CP bond to yield phosphate under phosphorus starvation conditions. These include the discovery of novel oxidative cleavage of the CP bond catalyzed by PhnY and PhnZ as well as phosphonohydrolases that liberate phosphate from phosphonoacetate. Perhaps the crown jewel of phosphonate catabolism has been the recent resolution of the longstanding problem of the C-P lyase responsible for reductively cleaving the CP bond of a number of different phosphonates to release phosphate. Taken together, the strides made on both metabolic and catabolic fronts illustrate an array of fascinating biochemistry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Selective extraction of hydrocarbons, phosphonates and phosphonic acids from soils by successive supercritical fluid and pressurized liquid extractions.

    Science.gov (United States)

    Chaudot, X; Tambuté, A; Caude, M

    2000-01-14

    Hydrocarbons, dialkyl alkylphosphonates and alkyl alkylphosphonic acids are selectively extracted from spiked soils by successive implementation of supercritical carbon dioxide, supercritical methanol-modified carbon dioxide and pressurized water. More than 95% of hydrocarbons are extracted during the first step (pure supercritical carbon dioxide extraction) whereas no organophosphorus compound is evidenced in this first extract. A quantitative extraction of phosphonates is achieved during the second step (methanol-modified supercritical carbon dioxide extraction). Polar phosphonic acids are extracted during a third step (pressurized water extraction) and analyzed by gas chromatography under methylated derivatives (diazomethane derivatization). Global recoveries for these compounds are close to 80%, a loss of about 20% occurring during the derivatization process (co-evaporation with solvent). The developed selective extraction method was successfully applied to a soil sample during an international collaborative exercise.

  15. Specific acyclic isoprenoids as biological markers of methanogenic bacteria in marine sediments.

    Science.gov (United States)

    Brassell, S C; Wardroper, A M; Thomson, I D; Maxwell, J R; Eglinton, G

    1981-04-23

    The widespread occurrence of extended hopanoids in sediments and petroleums illustrates the importance of bacterial lipid contributions to geological materials. In archaebacteria, however, hopanoids are absent; their role as structural components of biomembranes is fulfilled by acyclic isoprenoids. Recent studies of the lipid constituents of archaebacteria have greatly extended the range of acyclic isoprenoid skeletons known in organisms (Fig. 1). In particularly, isoprenoids with head-to-head linkages have been identified, and such compounds (for example, 3,7,11,15,18,22,26,30-octamethyldotriacontane, I) have been recognized in petroleum and as degradation products of Messel shale kerogen. Here we report the first recognition of 2,6,10,15,19-pentamethyleicosane (II), a known component of methanogens, in marine sediments of Recent to Cretaceous age (Table 1) and suggest that it and certain other acyclic isoprenoids may be used as biological markers for methanogens.

  16. Intramolecular cascade rearrangements of enynamine derived ketenimines: access to acyclic and cyclic amidines.

    Science.gov (United States)

    Chauhan, Dinesh Pratapsinh; Varma, Sreejith J; Gudem, Mahesh; Panigrahi, Nihar; Singh, Khushboo; Hazra, Anirban; Talukdar, Pinaki

    2017-06-07

    Copper-catalyzed reaction of enynamines with sulfonylazides provides acyclic and cyclic amidines. Nucleophilic addition of the tethered amino group on the in situ generated ketenimine forms a six-membered cyclic zwitterionic intermediate which facilitates migration of the tethered amino group to the C 5 -center giving the acyclic amidine. On the other hand, migration of a substituent on the amino group to C 2 - and C 4 -centers results in the formation of cyclic amidines. Computational studies were carried out to validate the mechanism which indicates that the product distribution of the process depends on the substitutions on the enynamine backbone.

  17. 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...

  18. Phosphonate removal from discharged circulating cooling water using iron-carbon micro-electrolysis.

    Science.gov (United States)

    Zhou, Zhen; Qiao, Weimin; Lin, Yangbo; Shen, Xuelian; Hu, Dalong; Zhang, Jianqiao; Jiang, Lu-Man; Wang, Luochun

    2014-01-01

    Phosphonate is a commonly used corrosion and scale inhibitor for a circulating cooling water (CCW) system. Its discharge could cause eutrophication of receiving waters. The iron-carbon (Fe/C) micro-electrolysis technology was used to degrade and remove phosphonate from discharged CCW. The influences of initial pH, Fe/C ratio (FCR) and temperature on phosphonate removal were investigated in a series of batch tests and optimized by response surface methodology. The quadratic model of phosphonate removal was obtained with satisfactory degrees of fitness. The optimum conditions with total phosphorus removal efficiency of 95% were obtained at pH 7.0, FCR of 1.25, and temperature of 45 °C. The phosphonate removal mechanisms were also studied. Phosphonate removal occurred predominantly via two consecutive reactive phases: the degradation of phosphonate complexes (Ca-phosphonate) and the precipitation of Fe/C micro-electrolysis products (PO₄(3-), Ca²⁺ and Fe³⁺).

  19. Experimental and theoretical studies on extraction of actinides and lanthanides by alicyclic H-phosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Annam, Suresh; Sivaramakrishna, Akella; Vijayakrishna, Kari [VIT Univ., Tamil Nadu (India). Dept. of Chemistry; Gopakumar, Gopinadhanpillai; Rao, C.V.S. Brahmmananda; Sivaraman, N. [Indira Gandhi Centre for Atomic Research (IGCAR), Tamil Nadu (India). Chemistry Group

    2017-06-01

    Three different alicyclic substituents H-phosphonates, namely, dicyclopentyl H-phosphonate, dicyclohexyl H-phosphonate and dimenthyl H-phosphonate were synthesized and used for liquid-liquid extraction of actinide elements (U, Am and Th) and lanthanide (Gd) in n-dodecane from nitric acid medium. The physicochemical properties of the extractants, such as density, viscosity, solubility were determined. At lower acidities, these H-phosphonates exhibit higher distribution values and the extraction following cation exchange mechanism through P-OH group of tri-coordinated phosphite form. At higher acidities (2N), the extraction is primarily via solvation mechanism through P=O group of penta-coordinated phosphonate form. Amongst the three H-phosphonates, examined dimenthyl H-phosphonate showed the best results for the actinide extraction. Density functional theory (DFT) calculations were applied to understand the electronic structure of the ligands and the metal complexes. The calculated large complexation energy of UO{sub 2}(NO{sub 3}){sub 2}.@2DMnHP is in agreement with the observed trend in experimental distribution ratio data.

  20. Phosphonates as alternative to tributyl phosphate for the separation of actinides from fission products

    International Nuclear Information System (INIS)

    Vyas, Chirag K.; Joshirao, Pranav M.; Manchanda, Vijay K.; Rao, C.V.S. Brahmmananda; Jayalakshmi, S.

    2015-01-01

    The present work investigates the role of increase in the basicity of organophosphorus extractant (dialkylalkyl phosphonates) on the uptake of actinides and fission products vis-a-vis tributyl phosphate (TBP), currently employed as a universal extractant. Two dialkylalkyl phosphonates viz. dibutylpropyl phosphonate (DBPrP) and dibutylpentyl phosphonate (DBPeP) were synthesized, characterized and evaluated for their solvent extraction behavior towards U(VI), Th(IV), Eu(III) and Tc(VII) in nitric acid medium ranging from 0.01-6 M. It was observed that increasing the basicity of the phosphoryl oxygen enhanced the uptake of the actinides and the distribution coefficient values were significantly larger as compared to TBP. The limiting organic concentration (LOC) value was estimated for Th(IV) for these extractants and compared with the TBP system. The separation factors of actinides with phosphonates over Tc(VII) are distinctly better than that with TBP.

  1. Synthesis of Ethylene diamine tetra methylene phosphonic acid EDTMP

    International Nuclear Information System (INIS)

    Assaad, Th.

    2009-06-01

    Ethylenediamine tetramethylene phosphonic acid (EDTMP) is one of the most widely used ligands which forms stable complexes with various radionuclides all of which have shown high bone affinity and other favorable pharmacological characteristics in biodistribution studies. The EDTMP is very important precursor in the preparation of radiopharmaceutical kits which is used in the applications for bone diagnosis and therapy was synthesized in one step with Mannich type reaction. The obtained product was fully characterized by its multi-nuclear NMR and IR spectroscopy. The purity of the product was confirmed by HPLC. (author)

  2. Surface functionalization of detonation nanodiamonds by phosphonic dichloride derivatives.

    Science.gov (United States)

    Presti, Charlene; Alauzun, Johan G; Laurencin, Danielle; Mutin, P Hubert

    2014-08-05

    A new method for the functionalization of detonation nanodiamonds (DNDs) is proposed, on the basis of surface modification with phosphonic dichloride derivatives. DNDs were first modified by phenylphosphonic dichloride, and the grafting modes and hydrolytic stability under neutral conditions were investigated using (1)H, (13)C, and (31)P solid state NMR spectroscopy, Fourier transform infrared spectroscopy, as well as elemental analysis. Then, in order to illustrate the possibilities offered by this method, DNDs functionalized by mesityl imidazolium groups were obtained by postmodification of DNDs modified by 12-bromododecylphosphonic dichloride. The oxidative thermal stability of the functionalized DNDs was investigated using thermogravimetric analysis.

  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. Existence principles for inclusions of Hammerstein type involving noncompact acyclic multivalued maps

    Directory of Open Access Journals (Sweden)

    Jean-Francois Couchouron

    2002-01-01

    Full Text Available We apply Monch type fixed point theorems for acyclic multivalued maps to the solvability of inclusions of Hammerstein type in Banach spaces. Our approach makes possible to unify and improve the existence theories for nonlinear evolution problems and abstract integral inclusions of Volterra and Fredholm type.

  5. A new recursive incremental algorithm for building minimal acyclic deterministic finite automata

    NARCIS (Netherlands)

    Watson, B.W.; Martin-Vide, C.; Mitrana, V.

    2003-01-01

    This chapter presents a new algorithm for incrementally building minimal acyclic deterministic finite automata. Such minimal automata are a compact representation of a finite set of words (e.g. in a spell checker). The incremental aspect of such algorithms (where the intermediate automaton is

  6. Metabolism of acyclic and cyclic N-nitroamines by cultured human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Harris, Curtis C.; Trump, Benjamin F.

    1978-01-01

    Cultured human colon mucosa was found to metabolize both acyclic and cyclic N-nitrosamines as measured by 14C-CO2 formation and reaction of the activated moieties with cellular macromolecules. Dimethylnitrosamine and N-nitrosopyrrolidine were metabolized by explants from all patients studied. A p...

  7. 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.

  8. 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...

  9. Lanthanide phosphonates: Synthesis, thermal stability and magnetic characterization

    Energy Technology Data Exchange (ETDEWEB)

    Amghouz, Z., E-mail: amghouz.uo@uniovi.es [Departamentos de Quimica Fisica y Analitica y Quimica Organica e Inorganica, Universidad de Oviedo - CINN, 33006 Oviedo (Spain); Garcia, J.R.; Garcia-Granda, S. [Departamentos de Quimica Fisica y Analitica y Quimica Organica e Inorganica, Universidad de Oviedo - CINN, 33006 Oviedo (Spain); Clearfield, A. [Department of Chemistry, Texas A and M University, College Station, TX 77842-3012 (United States); Rodriguez Fernandez, J.; Pedro, I. de [CITIMAC, Facultad de Ciencias, Universidad de Cantabria, 39005 Santander (Spain); Blanco, J.A. [Departamento de Fisica, Universidad de Oviedo, 33007 Oviedo (Spain)

    2012-09-25

    Highlights: Black-Right-Pointing-Pointer Report of the complete series of lanthanide 1,4-phenylbis(phosphonate). Black-Right-Pointing-Pointer Synthesis under conventional hydrothermal synthesis or microwave-assisted hydrothermal synthesis. Black-Right-Pointing-Pointer Cation size is the key factor for the structural and particles size variations. Black-Right-Pointing-Pointer Thermal behaviour is characterized by unusual very high thermal stability. - Abstract: Series of novel organic-inorganic hybrids materials based on trivalent lanthanides (Ln = Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) and 1,4-phenylbis(phosphonate) obtained under hydrothermal conditions either by oven heat or microwave irradiation. The anhydrous compounds containing La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, and Ho, are isostructural. However, the compounds based on Y, Er, Tm, Yb, and Lu are hydrated and their structures have not yet been solved. The series of compounds are characterized by PXRD, TEM, SEM-EDX and thermal analyses (TG-MS and DSC). TEM study show a variable particles size with a minimum mean-particle size of ca. 30 nm. These compounds exhibit unusual very high thermal stability. The size of particles and the thermal stability are depending on lanthanide(III) cation features. All the investigated materials show paramagnetic behaviour. The magnetic susceptibility data follow a Curie-Weiss laws with paramagnetic effective moments in good agreement with those expected for Ln{sup 3+} free ions.

  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. 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.

  12. 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.

  13. 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.

  14. Flame retardant cotton fabrics by electron beam-induced polymerization of vinyl phosphonate oligomer

    International Nuclear Information System (INIS)

    Sawai, Takeshi; Ametani, Kazuo; Enomoto, Ichiro

    1988-01-01

    Vinyl phosphonate oligomer is presently used commercially as a cellulosic flame retardant in conjugation with N-methylol acrylamide, using a persulfate catalyst and a thermal cure. This combination can also be cured at room temperature with electron beams, as can the vinyl phosphonate alone. For the textile application, fixation of flame retardants by electron beams with low energy is one of the most promising applications. For the purpose of preparing flame resistant cotton fabrics such as bed sheets and pajamas, flame retardant curing of vinyl phosphonate oligomer on cotton fabrics was examined using electron beams from a self-sealed electron beam processor and gamma rays from a 60 Co source. A joint investigation was undertaken by the Tokyo Metropolitan Textile Research Institute and Tokyo Metropolitan Isotope Research Center to determine the feasibility of curing vinyl phosphonate oligomer on the cotton fabrics for textile finishing. (author)

  15. Synthesis, self-assembly and lipoplex formulation of two novel cyclic phosphonate lipids

    Directory of Open Access Journals (Sweden)

    JenniferYeh

    2013-05-01

    Full Text Available Background: Synthetic cationic lipids hold much potential as gene packaging and delivery agents for the treatment of inherited and acquired life threatening diseases, such as cancer, AIDS, cardiovascular diseases, and certain autoimmune disorders. Methods: We report the synthesis, self-assembly as characterized by critical micelle concentrations and plasmid DNA gel retardation using two novel cyclic, phosphonate cationic lipids 2a and 2b, which were synthesized by derivatizing two diastereomeric macrocyclic phosphonates 1a and 1b with a 2-carbon hydroxylamine linker, N, N-dimethylethanolamine (3. Results: The production of cyclic phosphonate lipids 2a and 2b in 73% and 60% yields, respectively, was achieved using classical synthetic methods involving nucleophilic substitution at the phosphorus centre. Conclusions: The synthesis, aggregation and DNA binding properties of these novel cyclic phosphonate lipids suggest that they may have utility serving as gene packaging and delivery agents.

  16. Preliminary assessment of developmental toxicity of Perfluorinated Phosphonic Acid in mice

    Science.gov (United States)

    Perfluorinated phosphonic acids (PFPAs) are a third member of the perfluoroalkyl acid (PFAA) family, and are structurally similar to the perfluoroalkyl sulfonates and perfluoroalkyl carboxylates. These emerging chemicals have recently been detected in the environment, particularl...

  17. Ultrasound-assisted catalytic synthesis of acyclic imides in the presence of p-toluenesulfonic acid under solvent free conditions

    Directory of Open Access Journals (Sweden)

    Nasr-Esfahani Masoud

    2012-01-01

    Full Text Available A rapid and convenient preparation of acyclic imides by the reaction of aliphatic and aromatic nitriles with acyclic carboxylic anhydride in the presence of catalytic amounts of p-toluenesulfonic acid under thermal or ultrasonic conditions is reported. The advantages of this procedure are moderate reaction times, good to excellent yields, use of inexpensive and ecofriendly catalyst. The reaction of nitriles with aliphatic anhydrides proceeds in thermal conditions, while by the use of ultrasound irradiations these reactions get accelerated.

  18. Synthesis of 8-amino and 8-substituted amino derivatives of acyclic purine nucleoside and nucleotide analogs. Alkylation of 8-substituted purine bases

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko; Holý, Antonín

    2001-01-01

    Roč. 20, 4-7 (2001), s. 1103-1106 ISSN 1525-7770 R&D Projects: GA ČR GV203/96/K001 Institutional research plan: CEZ:AV0Z4055905 Keywords : nucleotide analogs Subject RIV: CC - Organic Chemistry Impact factor: 0.508, year: 2001

  19. New 2-alkynyl derivatives of the acyclic nucleoside 9-(2,3-dihydroxypropyl)adenine and their 6-guanidinopurine counterparts as potential effectors of adenosine receptors

    Czech Academy of Sciences Publication Activity Database

    Česnek, Michal; Holý, Antonín; Masojídková, Milena

    2003-01-01

    Roč. 68, č. 11 (2003), s. 2201-2218 ISSN 0010-0765 R&D Projects: GA AV ČR IBS4055109; GA MŠk OC D13.20 Institutional research plan: CEZ:AV0Z4055905 Keywords : adenosine receptors * alkynes * purines Subject RIV: CC - Organic Chemistry Impact factor: 1.041, year: 2003

  20. Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs

    Czech Academy of Sciences Publication Activity Database

    Špaček, Petr; Keough, D. T.; Chavchich, M.; Dračínský, Martin; Janeba, Zlatko; Naesens, L.; Edstein, M. D.; Guddat, L. W.; Hocková, Dana

    2017-01-01

    Roč. 25, č. 15 (2017), s. 4008-4030 ISSN 0968-0896 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : enzyme inhibitors * nucleotide analogues * malaria Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.930, year: 2016

  1. Fluoride-Mediated Dephosphonylation of α-Diazo-β-carbonyl Phosphonates.

    Science.gov (United States)

    Phatake, Ravindra S; Mullapudi, Venkannababu; Wakchaure, Vivek C; Ramana, Chepuri V

    2017-01-20

    The possibility of fluoride-mediated selective dephosphonylation of α-diazo-β-carbonyl phosphonates such as the Ohira-Bestmann reagent has been proposed and executed. The resulting α-diazocarbonyl intermediates undergo a (3 + 2)-cycloaddition at room temperature with conjugated olefins and benzynes. Interestingly, under the current conditions, the resulting cycloaddition products underwent either N-acylation (with excess α-diazo-β-carbonyl phosphonates) or Michael addition (with conjugated olefins).

  2. Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage

    Czech Academy of Sciences Publication Activity Database

    Králíková, Šárka; Buděšínský, Miloš; Barvík, I.; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

    2011-01-01

    Roč. 30, 7/9 (2011), s. 524-543 ISSN 1525-7770 R&D Projects: GA ČR GA202/09/0193; GA AV ČR KAN200520801; GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z40550506 Keywords : alpha-hydroxy-phosphonate linkage * ApA analogues * phosphonate internucleotide bond * NMR conformational study Subject RIV: CC - Organic Chemistry Impact factor: 0.899, year: 2011

  3. Nanocomposites of phosphonic-acid-functionalized polyethylenes with inorganic quantum dots.

    Science.gov (United States)

    Rünzi, Thomas; Baier, Moritz C; Negele, Carla; Krumova, Marina; Mecking, Stefan

    2015-01-01

    Insertion of diethyl vinyl phosphonates and free vinyl phosphonic acid, respectively, into [(P^O)Pd(Me)(dmso)] ((P^O) = κ(2)-P,O-Ar2PC6H4SO2O with Ar = 2-MeOC6H4) (1-dmso) occurs in a 2,1- as well as 1,2-fashion, to form a four-and a five-membered chelate [(P^O)Pd{κ(2)-C,O-CH(P(O)(OR)2)CH2CH3}] and [(P^O)Pd{κ(2)-C,O-CH2CH(P(O)(OR)2)CH3}] (R = H, Et). No decomposition or other reactions of 1 by free phosphonic acid moieties occur. Copolymerization in a pressure reactor by 1-dmso yields linear random poly(ethylene-co-diethyl vinyl phosphonate) and poly(ethylene-co-vinyl phosphonic acid). In these copolymerizations, reversible coordination of the phosphonate moieties of free monomer as well as chelate formation by incorporated monomer retards chain growth as also evidenced by relative binding studies of diethyl phosphonate towards 1. Post-polymerization emulsification of poly(ethylene-co-vinyl phosphonic acid) together with CdSe/CdS quantum dots (QDs) yields submicron (ca. 50 nm from dynamic light scattering (DLS) and transmission electron microscopy (TEM)) polymer particles with the QDs embedded in the functionalized polyethylene in a nonaggregated fashion. This embedding benefits the fluorescence behavior in terms of continuous emission and life-time as revealed by wide-field fluorescence measurements. These composite particle dispersions are employed as a ″masterbatch" together with an aqueous high density polyethylene (HDPE) dispersion to generate thin films (by spin-coating) and bulk materials (from the melt), respectively, in which the inorganic nanoparticles remain highly disperse. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Acyclic Ketones in the Defensive Secretion of a “Daddy Longlegs” (Leiobunum vittatum)

    Science.gov (United States)

    Meinwald, J.; Kluge, A. F.; Carrel, J. E.; Eisner, T.

    1971-01-01

    The defensive secretion of the “daddy longlegs” Leiobunum vittatum was analyzed and found to contain the acyclic ketones 4-methylheptan-3-one and E-4,6-dimethyl-6-octen-3-one as its major organic components. Although 4-methylheptan-3-one has been found previously as an alarm substance in certain ant genera, the second component, whose structure is confirmed by synthesis, is new. PMID:5283937

  5. Acyclic ketones in the defensive secretion of a "daddy longlegs" (Leiobunum vittatum).

    Science.gov (United States)

    Meinwald, J; Kluge, A F; Carrel, J E; Eisner, T

    1971-07-01

    The defensive secretion of the "daddy longlegs" Leiobunum vittatum was analyzed and found to contain the acyclic ketones 4-methylheptan-3-one and E-4,6-dimethyl-6-octen-3-one as its major organic components. Although 4-methylheptan-3-one has been found previously as an alarm substance in certain ant genera, the second component, whose structure is confirmed by synthesis, is new.

  6. Characterization of E and Z isomers in macrocyclic lactones and acyclic pheromones by NMR spectra

    International Nuclear Information System (INIS)

    Mahajan, J.R.; Resck, I.S.; Braz Filho, R.; Carvalho, M.G. de

    1995-01-01

    A large proportion of pheromones, isolated from a variety of insects, constitutes a big list of diversely functionalized acyclic compounds, which have been synthesized by several routes. Catalytic or chemical methods were examined for the Z to E isomerization and their efficiency checked by 1 H and 13 C NMR spectra. Nuclear magnetic resonance has been used to identify and characterize molecular structure of the compounds, besides chemical shifts was analysed

  7. Pd-catalyzed Suzuki-Miyaura coupling reaction in the synthesis of 5-aryl-1-[2-(phosphonomethoxy)ethyl]uracils as potential multisubstrate inhibitors of thymidine phosphorylase

    Czech Academy of Sciences Publication Activity Database

    Pomeisl, Karel; Holý, Antonín; Pohl, Radek

    2007-01-01

    Roč. 48, č. 17 (2007), s. 3065-3067 ISSN 0040-4039 R&D Projects: GA MŠk 1M0508 Grant - others:Descartes Prize(XE) HPAW-CT-2002-9001 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * thymidine phosphorylase * Suzuki coupling * pyrimidine Subject RIV: CC - Organic Chemistry Impact factor: 2.615, year: 2007

  8. 5-Azacytosine compounds in medicinal chemistry: current stage and future perspectives

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Otmar, Miroslav

    2012-01-01

    Roč. 4, č. 8 (2012), s. 991-1005 ISSN 1756-8919 R&D Projects: GA MPO FR-TI4/625 Institutional support: RVO:61388963 Keywords : 5-azacytidine * 2´-deoxy-5-azacytidine * hypomethylation * DAC * epigenetics * DNA methylation * acyclic nucleoside phosphonates * 5-azacytosine * HPMP-5-azacytosine * prodrugs Subject RIV: CC - Organic Chemistry Impact factor: 3.310, year: 2012

  9. Synthesis of purine N9-[2-hydroxy-3-O-(phosphonomethoxy)propyl] derivatives and their side-chain modified analogues as potential antimalarial agents

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Dračínský, Martin; Hocková, Dana; Holý, Antonín; Keough, D. T.; Guddat, L. W.

    2012-01-01

    Roč. 20, č. 3 (2012), s. 1222-1230 ISSN 0968-0896 R&D Projects: GA MŠk 1M0508; GA ČR GAP207/11/0108 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * Malaria * Plasmodium falciparum * Plasmodium vivax * hypoxanthine-guanine-(xanthine)-phosphoribosyltransferase Subject RIV: CC - Organic Chemistry Impact factor: 2.903, year: 2012

  10. 4-Toluenesulfonyloxymethyl-(H)-phosphinate: A Reagent for the Introduction of O- and S-Methyl-(H)-phosphinate Moieties

    Czech Academy of Sciences Publication Activity Database

    Kostov, Ondřej; Páv, Ondřej; Buděšínský, Miloš; Liboska, Radek; Šimák, Ondřej; Petrová, Magdalena; Novák, Pavel; Rosenberg, Ivan

    2016-01-01

    Roč. 18, č. 11 (2016), s. 2704-2707 ISSN 1523-7060 R&D Projects: GA ČR GA13-26526S; GA MZd NV15-31604A; GA TA ČR TA03010598; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * phosphinyl dipeptide isosteres * efficient synthesis Subject RIV: CC - Organic Chemistry Impact factor: 6.579, year: 2016

  11. Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines

    Czech Academy of Sciences Publication Activity Database

    Balzarini, J.; Schols, D.; Van Laethem, K.; De Clercq, E.; Hocková, Dana; Masojídková, Milena; Holý, Antonín

    2007-01-01

    Roč. 59, č. 1 (2007), s. 80-86 ISSN 0305-7453 R&D Projects: GA MŠk 1M0508; GA AV ČR IBS4055109; GA AV ČR 1QS400550501 Grant - others:ISEP/FORTIS(XE) GOA/2005/19 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antiretroviral drugs * HIV * MSV * PMEO-DAPy Subject RIV: CC - Organic Chemistry Impact factor: 4.038, year: 2007

  12. Crystal structures and inhibition of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase

    Czech Academy of Sciences Publication Activity Database

    Terán, D.; Hocková, Dana; Česnek, Michal; Zíková, Alena; Naesens, L.; Keough, D. T.; Guddat, L. W.

    2016-01-01

    Roč. 6, Oct 27 (2016), č. článku 35894. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA16-06049S; GA MŠk LL1205 Institutional support: RVO:61388963 ; RVO:60077344 Keywords : enzyme inhibitors * acyclic nucleoside phosphonates * HGPRT Subject RIV: CC - Organic Chemistry; EE - Microbiology, Virology (BC-A) Impact factor: 4.259, year: 2016 http://www.nature.com/articles/srep35894

  13. 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

  14. 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.

  15. The inhibition of crystal growth of mirabilite in aqueous solutions in the presence of phosphonates

    Science.gov (United States)

    Vavouraki, A. I.; Koutsoukos, P. G.

    2016-02-01

    The formation of sodium sulfate decahydrate (Mirabilite) has been known to cause serious damages to structural materials both of modern and of historical buildings. Methods which can retard or completely suppress the development of mirabilte crystals are urgently needed especially as remedies or preventive measures for the preservation of the built cultural heritage. In the present work we present results on the effect of the presence of phosphonate compounds on the kinetics of crystal growth from aqueous supersaturated solutions at 18 °C using the seeded growth technique. The phosphonate compounds tested differed with respect to the number of ionizable phosphonate groups and with respect to the number of amino groups in the respective molecules. The crystal growth process was monitored by the temperature changes during the exothermic crystallization of mirabilite in the stirred supersaturated solutions. The crystal growth of mirabilite in the presence of: (1-hydroxyethylidene)-1, 1-diphosphonic acid (HEDP), amino tri (methylene phosphonic acid) (ATMP), hexamethylenediaminetetra (methylene)phosphonic acid (HTDMP), and diethylene triamine penta(methylene phosphonic acid)(DETPMP) over a range of concentrations between 0.1-5% w/w resulted in significant decrease of the rates of mirabilite crystal growth. All phosphonic compounds tested reduced the crystallization rates up to 60% in comparison with additive-free solutions. The presence of the test compounds did not cause changes of the mechanism of crystal growth which was surface diffusion controlled, as shown by the second order dependence of the rates of mirabilite crystal growth on the relative supersaturation. The excellent fit of the measured rates to a kinetic Langmuir-type model suggested that the activity of the tested inhibitors could be attributed to the adsorption and subsequent reduction of the active crystal growth sites of the seed crystals. In all cases, the inhibitory activity was reduced with

  16. Oxygen isotope signature of UV degradation of glyphosate and phosphonoacetate: Tracing sources and cycling of phosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Sandy, Edward H. [State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan 430074 (China); Department of Geology and Geophysics, Yale University, P.O. Box 208109, New Haven, CT 06520-8109 (United States); Department of Chemistry, University of Sierra Leone, Freetown (Sierra Leone); Blake, Ruth E., E-mail: ruth.blake@yale.edu [Department of Geology and Geophysics, Yale University, P.O. Box 208109, New Haven, CT 06520-8109 (United States); School of Civil and Environmental Engineering, and National “International Cooperation Base on Environment and Energy”, University of Science and Technology Beijing, Beijing 100084 (China); Chang, Sae Jung [Department of Geology and Geophysics, Yale University, P.O. Box 208109, New Haven, CT 06520-8109 (United States); Jun, Yao, E-mail: yaojun@ustb.edu.cn [State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan 430074 (China); Department of Geology and Geophysics, Yale University, P.O. Box 208109, New Haven, CT 06520-8109 (United States); School of Civil and Environmental Engineering, and National “International Cooperation Base on Environment and Energy”, University of Science and Technology Beijing, Beijing 100084 (China); Yu, Chan [Department of Geology and Geophysics, Yale University, P.O. Box 208109, New Haven, CT 06520-8109 (United States); School of Civil and Environmental Engineering, and National “International Cooperation Base on Environment and Energy”, University of Science and Technology Beijing, Beijing 100084 (China)

    2013-09-15

    Highlights: • Phosphonate (phon) hydrolysis by UVR (1.2 kW) attained ≥90% completion in 84 h. • Isotope study reveals both ambient H{sub 2}O and O{sub 2} involvements in phon C-P bond cleavage. • Mechanistic models proposed for phon C-P bond cleavage based on O-isotope analysis. • Model equations used to calculate δ{sup 18}O{sub P-org} of original phon P-moiety-useful as a tracer. • Study shows relevance in tracing phon sources and cycling in the environment. -- Abstract: The degradation of phosphonates in the natural environment constitutes a major route by which orthophosphate (Pi) is regenerated from organic phosphorus and recently implicated in marine methane production, with ramifications to environmental pollution issues and global climate change concerns. This work explores the application of stable oxygen isotope analysis in elucidating the C-P bond cleavage mechanism(s) of phosphonates by UV photo-oxidation and for tracing their sources in the environment. The two model phosphonates used, glyphosate and phosphonoacetic acid were effectively degraded after exposure to UV irradiation. The isotope results indicate the involvement of both ambient water and atmospheric oxygen in the C-P bond cleavage and generally consistent with previously posited mechanisms of UV-photon excitation reactions. A model developed to calculate the oxygen isotopic composition of the original phosphonate P-moiety, shows both synthetic phosphonates having distinctly lower values compared to naturally derived organophosphorus compounds. Such mechanistic models, based on O-isotope probing, are useful for tracing the sources and reactions of phosphonates in the environment.

  17. Novel quinolinone-phosphonic acid AMPA antagonists devoid of nephrotoxicity.

    Science.gov (United States)

    Cordi, Alex A; Desos, Patrice; Ruano, Elisabeth; Al-Badri, Hashim; Fugier, Claude; Chapman, Astrid G; Meldrum, Brian S; Thomas, Jean-Yves; Roger, Anita; Lestage, Pierre

    2002-10-01

    We reported previously the synthesis and structure-activity relationships (SAR) in a series of 2-(1H)-oxoquinolines bearing different acidic functions in the 3-position. Exploiting these SAR, we were able to identify 6,7-dichloro-2-(1H)-oxoquinoline-3-phosphonic acid compound 3 (S 17625) as a potent, in vivo active AMPA antagonist. Unfortunately, during the course of the development, nephrotoxicity was manifest at therapeutically effective doses. Considering that some similitude exists between S 17625 and probenecid, a compound known to protect against the nephrotoxicity and/or slow the clearance of different drugs, we decided to synthesise some new analogues of S 17625 incorporating some of the salient features of probenecid. Replacement of the chlorine in position 6 by a sulfonylamine led to very potent AMPA antagonists endowed with good in vivo activity and lacking nephrotoxicity potential. Amongst the compounds evaluated, derivatives 7a and 7s appear to be the most promising and are currently evaluated in therapeutically relevant stroke models.

  18. Determination of perfluoroalkyl carboxylic, sulfonic, and phosphonic acids in food.

    Science.gov (United States)

    Ullah, Shahid; Alsberg, Tomas; Vestergren, Robin; Berger, Urs

    2012-11-01

    A sensitive and accurate method was developed and validated for simultaneous analysis of perfluoroalkyl carboxylic acids, sulfonic acids, and phosphonic acids (PFPAs) at low picograms per gram concentrations in a variety of food matrices. The method employed extraction with acetonitrile/water and cleanup on a mixed-mode co-polymeric sorbent (C8 + quaternary amine) using solid-phase extraction. High-performance liquid chromatographic separation was achieved on a C18 column using a mobile phase gradient containing 5 mM 1-methyl piperidine for optimal chromatographic resolution of PFPAs. A quadrupole time-of-flight high-resolution mass spectrometer operating in negative ion mode was used as detector. Method detection limits were in the range of 0.002 to 0.02 ng g(-1) for all analytes. Sample preparation (extraction and cleanup) recoveries at a spiking level of 0.1 ng g(-1) to a baby food composite were in the range of 59 to 98 %. A strong matrix effect was observed in the analysis of PFPAs in food extracts, which was tentatively assigned to sorption of PFPAs to the injection vial in the solvent-based calibration standard. The method was successfully applied to a range of different food matrices including duplicate diet samples, vegetables, meat, and fish samples.

  19. Phosphonic Acids for Interfacial Engineering of Transparent Conductive Oxides

    KAUST Repository

    Paniagua, Sergio A.

    2016-05-26

    Transparent conducting oxides (TCOs), such as indium tin oxide and zinc oxide, play an important role as electrode materials in organic-semiconductor devices. The properties of the inorganic-organic interface - the offset between the TCO Fermi level and the relevant transport level, the extent to which the organic semiconductor can wet the oxide surface, and the influence of the surface on semiconductor morphology - significantly affect device performance. This review surveys the literature on TCO modification with phosphonic acids (PAs), which has increasingly been used to engineer these interfacial properties. The first part outlines the relevance of TCO surface modification to organic electronics, surveys methods for the synthesis of PAs, discusses the modes by which they can bind to TCO surfaces, and compares PAs to alternative organic surface modifiers. The next section discusses methods of PA monolayer deposition, the kinetics of monolayer formation, and structural evidence regarding molecular orientation on TCOs. The next sections discuss TCO work-function modification using PAs, tuning of TCO surface energy using PAs, and initiation of polymerizations from TCO-tethered PAs. Finally, studies that examine the use of PA-modified TCOs in organic light-emitting diodes and organic photovoltaics are compared. © 2016 American Chemical Society.

  20. Phosphonic Acids for Interfacial Engineering of Transparent Conductive Oxides

    KAUST Repository

    Paniagua, Sergio A.; Giordano, Anthony J.; Smith, O’ Neil L.; Barlow, Stephen; Li, Hong; Armstrong, Neal R.; Pemberton, Jeanne E.; Bredas, Jean-Luc; Ginger, David; Marder, Seth R.

    2016-01-01

    Transparent conducting oxides (TCOs), such as indium tin oxide and zinc oxide, play an important role as electrode materials in organic-semiconductor devices. The properties of the inorganic-organic interface - the offset between the TCO Fermi level and the relevant transport level, the extent to which the organic semiconductor can wet the oxide surface, and the influence of the surface on semiconductor morphology - significantly affect device performance. This review surveys the literature on TCO modification with phosphonic acids (PAs), which has increasingly been used to engineer these interfacial properties. The first part outlines the relevance of TCO surface modification to organic electronics, surveys methods for the synthesis of PAs, discusses the modes by which they can bind to TCO surfaces, and compares PAs to alternative organic surface modifiers. The next section discusses methods of PA monolayer deposition, the kinetics of monolayer formation, and structural evidence regarding molecular orientation on TCOs. The next sections discuss TCO work-function modification using PAs, tuning of TCO surface energy using PAs, and initiation of polymerizations from TCO-tethered PAs. Finally, studies that examine the use of PA-modified TCOs in organic light-emitting diodes and organic photovoltaics are compared. © 2016 American Chemical Society.

  1. Synthesis and applications of gem-bis-phosphonates, powerful complexing agents of metals

    International Nuclear Information System (INIS)

    Lecercle, D.

    2007-12-01

    This thesis was devoted to the development of new ways to prepare gem-bis-phosphonates compounds (BPs), and was carried out under the Program of Nuclear and Environmental Toxicology (ToxNuc-E). Two applications of these compounds have been investigated, the preparation of potent ligands of the uranyl ion for a target of decorporation, and the preparation of new anticancer compounds. The first of these applications was the consequence of work done in the laboratory, that have shown the strong uranium-binding properties of bis-phosphonic ligands. The in vivo tests performed on these compounds have shown the tendency of these ligands to cause liver accumulation of uranium, we wanted to address this problem by modifying the method of anchoring of the bis-phosphonates functions. To this end we have developed a new way to access to these compounds using a metal-carbenoid mediated poly-ols and poly-amines insertion, the metal-carbenoid species bearing the bis-phosphonate function. Regarding the preparation of BPs as anticancer agents, we have developed a new synthetic pathway using a phosphine catalyzed α-P addition of phosphorated pro-nucleophiles to alkynyl-phosphonates as a key step. This enabled us to prepare thirty compound whose activity was evaluated on two cell lines (A431 and HuH7). Five of these compounds possess an activity equivalent to that of the compound described as the most active, the Zoledronate. (author)

  2. Anti-HIV therapy with AZT prodrugs: AZT phosphonate derivatives, current state and prospects.

    Science.gov (United States)

    Khandazhinskaya, Anastasiya; Matyugina, Elena; Shirokova, Elena

    2010-06-01

    AIDS, a disease caused by human immunodeficiency virus, was called 'plague of the twentieth century'. 3'-Azido-3'-deoxythymidine (AZT), the first compound approved for the treatment of HIV, is still a mandatory component of treatment schemes. However, its toxicity stimulated a search for new agents. This review presents the history and current state of the design of AZT prodrugs based on its phosphonate derivatives. Although every effort was made to include as many AZT structures bearing phosphonate residues and demonstrate the variety they offer, we also concentrated on the studies performed in our laboratory. Special attention was also paid to AZT 5'-H-phosphonate (phosphazide, Nikavir) approved in the Russian Federation as a drug for the prevention and treatment of HIV infection. The prodrug strategy applied to AZT phosphonate derivatives enriched chemistry, biology and medicine not only with new knowledge, methods and structures, but also with a new anti-HIV drug Nikavir. Currently, study of another phosphonate, AZT 5'-aminocarbonylphosphonate, is underway. Slow release of AZT following oral administration and penetration into cells, decreased toxicity and the lack of cumulative properties make the compounds of this group promising as extended-release forms of AZT.

  3. NMR studies of abasic sites in DNA duplexes: Deoxyadenosine stacks into the helix opposite acyclic lesions

    International Nuclear Information System (INIS)

    Kalnik, M.W.; Chang, Chienneng; Johnson, F.; Grollman, A.P.; Patel, D.J.

    1989-01-01

    Proton and phosphorus NMR studies are reported for two complementary nonanucleotide duplexes containing acyclic abasic sites. The first duplex, d(C-A-T-G-A-G-T-A-C)·d(G-T-A-C-P-C-A-T-G), contains an acyclic propanyl moiety, P, located opposite a deoxyadenosine at the center of the helix (designated AP P 9-mer duplex). The second duplex, d(C-A-T-G-A-G-T-A-C-)·d(G-T-A-C-E-C-A-T-G), contains a similarly located acyclic ethanyl moiety, E (designated AP E 9-mer duplex). The ethanyl moiety is one carbon shorter than the natural carbon-phosphodiester backbone of a single nucleotide unit of DNA. The majority of the exchangeable and nonexchangeable base and sugar protons in both the AP P 9-mer and AP E 9-mer duplexes, including those at the abasic site, have been assigned by recording and analyzing two-dimensional phase-sensitive NOESY data sets in H 2 O and D 2 O solution between -5 and 5 degree C. These spectroscopic observations establish that A5 inserts into the helix opposite the abasic site (P14 and El14) and stacks between the flanking G4·C15 and G6·C13 Watson-Crick base pairs in both the AP P 9-mer and AP E 9-mer duplexes. Proton NMR parameters for the Ap P 9-mer and AP E 9-mer duplexes are similar to those reported previously. These proton NMR experiments demonstrate that the structures at abasic sites are very similar whether the five-membered ring is open or closed or whether the phosphodiester backbone is shortened by one carbon atom. Phosphorus spectra of the AP P 9-mer and AP E 9-mer duplexes (5 degree C) indicate that the backbone conformation is similarly perturbed at three phosphodiester backbone torsion angles

  4. Diurnal rhythms in gonadotropins and progesterone in lactating and photoperiod induced acyclic hamsters

    International Nuclear Information System (INIS)

    Bridges, R.S.; Goldman, B.D.

    1975-01-01

    Levels of LH, FSH, and progesterone in serum were measured in lactating hamsters and in hamsters in which acyclicity was induced with altered photoperiod. Lactating hamsters were found to have low titers of LH, FSH, and progesterone in serum at 0900 (lights on 0500--1900) on Days 4, 9, 14, and 19 of lactation and increased levels of these hormones at 1600. Levels of LH and FSH in serum at both 0900 and 1600 remained relatively constant throughout lactation. In contrast, levels of progesterone in serum obtained at both 0900 and 1600 sampling times increased as lactation progressed. Ovariectomy on Day 9 of lactation reduced serum levels of progesterone at both 0900 and 1600 and eliminated the afternoon surge in progesterone in animals bled 5 days after surgery. The levels and pattern of LH in serum remained unchanged after ovariectomy in lactating hamsters. However, serum FSH levels in the ovariectomized, lactating animals were elevated at both 0900 and 1600 when compared to levels present in intact, lactating hamsters bled at the same times. Females which were acyclic due to altered photoperiod displayed similar patterns of LH, FSH, and progesterone in serum. Levels of LH, FSH, and progesterone in serum were low at 1000 (lights on 0500--1500) and were increased 2 to 10 fold at 1500. Ovariectomy was followed by lower progesterone levels in serum at 1000 and 1500 and eliminated the afternoon rise of this hormone. Serum levels of LH were unaffected by ovariectomy. As in lactating hamsters, levels of FSH in serum were elevated 3--4 days following ovariectomy at both bleeding times, but the levels were higher at 1500. These results indicate that acyclicity induced by lactation or exposure to a short photoperiod is characterized by similar diurnal patterns of circulating hormones in the hamster

  5. 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

  6. Reaction of acyclic enaminones with methoxymethylene meldrum's acid: synthetic and structural implications

    OpenAIRE

    Cunha,Silvio; Silva,Viviane C. da; Napolitano,Hamilton B.; Lariucci,Carlito; Vencato,Ivo

    2003-01-01

    The reaction of acyclic enaminones with methoxymethylene Meldrum's acid afforded N-adduct and/or C-adduct of enaminones in moderate to good yields. The regiochemistry of this reaction depends on the N-amino substituent of the enaminone. The C-adduct is a precursor to 2-pyridones. X-ray analysis of two N-adducts were investigated and the Z-s-Z configuration assigned. A reação de enaminonas com o derivado metoximetilênico do ácido de Meldrum forneceu N-adutos e/ou C-adutos das enaminonas, em...

  7. Competitive solvent extraction of alkaline-earth cations into chloroform by lipophilic acyclic polyether dicarboxylic acids

    International Nuclear Information System (INIS)

    Kang, S.I.; Czech, A.; Czech, B.P.; Stewart, L.E.; Bartsch, R.A.

    1985-01-01

    Competitive solvent extraction of alkaline-earth cations from aqueous solutions into chloroform by a series of lipophilic acyclic polyether dicarboxylic acids is reported. The influence of polyether chain length and of terminal carboxylic acid group variation upon extraction selectivity and efficiency is assessed. In the competitive extraction of concentrated magnesium, calcium, strontium and barium chloride solutions, one complexing agent exhibits pronounced selectivity for barium with Ba 2+ /S 2+ = 50, Ba 2+ /Ca 2+ = 250, and no detectable Mg 2+ extraction. 20 references, 3 figures, 1 table

  8. Preparation of polyvinyl alcohol graphene oxide phosphonate film and research of thermal stability and mechanical properties.

    Science.gov (United States)

    Li, Jihui; Song, Yunna; Ma, Zheng; Li, Ning; Niu, Shuai; Li, Yongshen

    2018-05-01

    In this article, flake graphite, nitric acid, peroxyacetic acid and phosphoric acid are used to prepare graphene oxide phosphonic and phosphinic acids (GOPAs), and GOPAs and polyvinyl alcohol (PVA) are used to synthesize polyvinyl alcohol graphene oxide phosphonate and phosphinate (PVAGOPs) in the case of faint acidity and ultrasound irradiation, and PVAGOPs are used to fabricate PVAGOPs film, and the structure and morphology of GOPAs, PVAGOPs and PVAGOPs film are characterized, and the thermal stability and mechanical properties of PVAGOPs film are investigated. Based on these, it has been proved that GOPAs consist of graphene oxide phosphonic acid and graphene oxide phosphinic acid, and there are CP covalent bonds between them, and PVAGOPs are composed of GOPAs and PVA, and there are six-member lactone rings between GOPAs and PVA, and the thermal stability and mechanical properties of PVAGOPs film are improved effectively. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Titanium-Phosphonate-Based Metal-Organic Frameworks with Hierarchical Porosity for Enhanced Photocatalytic Hydrogen Evolution

    KAUST Repository

    Li, Hui

    2018-02-01

    Photocatalytic hydrogen production is crucial for solar-to-chemical conversion process, wherein high-efficiency photocatalysts lie in the heart of this area. Herein a new photocatalyst of hierarchically mesoporous titanium-phosphonate-based metal-organic frameworks, featuring well-structured spheres, periodic mesostructure and large secondary mesoporosity, are rationally designed with the complex of polyelectrolyte and cathodic surfactant serving as the template. The well-structured hierarchical porosity and homogeneously incorporated phosphonate groups can favor the mass transfer and strong optical absorption during the photocatalytic reactions. Correspondingly, the titanium phosphonates exhibit significantly improved photocatalytic hydrogen evolution rate along with impressive stability. This work can provide more insights into designing advanced photocatalysts for energy conversion and render a tunable platform in photoelectrochemical field.

  10. Titanium-Phosphonate-Based Metal-Organic Frameworks with Hierarchical Porosity for Enhanced Photocatalytic Hydrogen Evolution

    KAUST Repository

    Li, Hui; Sun, Ying; Yuan, Zhong-Yong; Zhu, Yun-Pei; Ma, Tianyi

    2018-01-01

    Photocatalytic hydrogen production is crucial for solar-to-chemical conversion process, wherein high-efficiency photocatalysts lie in the heart of this area. Herein a new photocatalyst of hierarchically mesoporous titanium-phosphonate-based metal-organic frameworks, featuring well-structured spheres, periodic mesostructure and large secondary mesoporosity, are rationally designed with the complex of polyelectrolyte and cathodic surfactant serving as the template. The well-structured hierarchical porosity and homogeneously incorporated phosphonate groups can favor the mass transfer and strong optical absorption during the photocatalytic reactions. Correspondingly, the titanium phosphonates exhibit significantly improved photocatalytic hydrogen evolution rate along with impressive stability. This work can provide more insights into designing advanced photocatalysts for energy conversion and render a tunable platform in photoelectrochemical field.

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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....

  16. Phosphonate self-assembled monolayers on aluminum surfaces

    International Nuclear Information System (INIS)

    Hoque, E.; DeRose, J.A.; Hoffmann, P.; Mathieu, H.J.; Bhushan, B.; Cichomski, M.

    2006-01-01

    Substrates of aluminum (Al) deposited by physical vapor deposition onto Si substrates and then chemically reacted with perfluorodecylphosphonic acid (PFDP/Al/Si), decylphosphonic acid (DP/Al/Si), and octadecylphosphonic acid (ODP/Al/Si) were studied by x-ray photoelectron spectroscopy (XPS), contact angle measurements, atomic force microscopy (AFM), and friction force microscopy, a derivative of AFM, to characterize their surface chemical composition, roughness, and micro-/nanotribological properties. XPS analysis confirmed the presence of perfluorinated and nonperfluorinated alkylphosphonate molecules on the PFDP/Al/Si, DP/Al/Si, and ODP/Al/Si. The sessile drop static contact angle of pure water on PFDP/Al/Si was typically more than 130 deg. and on DP/Al/Si and ODP/Al/Si typically more than 125 deg. indicating that all phosphonic acid reacted Al/Si samples were very hydrophobic. The surface roughness for PFDP/Al/Si, DP/Al/Si, ODP/Al/Si, and bare Al/Si was approximately 35 nm as determined by AFM. The surface energy for PFDP/Al/Si was determined to be approximately 11 mN/m by the Zisman plot method compared to 21 and 20 mN/m for DP/Al/Si and ODP/Al/Si, respectively. Tribology involves the measure of lateral forces due to friction and adhesion between two surfaces. Friction, adhesion, and wear play important roles in the performance of micro-/nanoelectromechanical systems. PFDP/Al/Si gave the lowest adhesion and coefficient of friction values while bare Al/Si gave the highest. The adhesion and coefficient of friction values for DP/Al/Si and ODP/Al/Si were comparable

  17. 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.

  18. Limitations in determining enantiomeric excess of alcohols by 31 P-NMR of the phosphonate derivatives

    International Nuclear Information System (INIS)

    Laverde Junior, Antonio; Conceicao, Jelson J.A. da; Pilli, Ronaldo A.; Marsaioli, Anita J.; Miranda, Domingos S. de; Schirmer, Heiko; Meijere, Armin de

    1999-01-01

    The use of diastereomeric alcohol dialkyl-phosphonate derivatives to determine the enantiomeric excesses via 31 P-NMR signal ratios of anisochronous meso and threo isomers was successfully applied to secondary alcohols (Feringa's method). Expansion of the methodology to primary alcohols processing the hydroxyl groups tethered to the stereogenic centers by two or more methylene groups proved the method to be inefficient. The comparison between the coupled and decoupled spectra is important in order to identify the signals corresponding to the dialkyl-phosphonates. Nevertheless the methodology should be applied whenever the amount of the alcohol and its structure are not the limiting factors. (author)

  19. Yield Improvement and Energy Savings Uing Phosphonates as Additives in Kraft pulping

    Energy Technology Data Exchange (ETDEWEB)

    Ulrike W. Tschirner; Timothy Smith

    2007-03-31

    Project Objective: Develop a commercially viable modification to the Kraft process resulting in energy savings, increased yield and improved bleachability. Evaluate the feasibility of this technology across a spectrum of wood species used in North America. Develop detailed fundamental understanding of the mechanism by which phosphonates improve KAPPA number and yield. Evaluate the North American market potential for the use of phosphonates in the Kraft pulping process. Examine determinants of customer perceived value and explore organizational and operational factors influencing attitudes and behaviors. Provide an economic feasibility assessment for the supply chain, both suppliers (chemical supply companies) and buyers (Kraft mills). Provide background to most effectively transfer this new technology to commercial mills.

  20. Reaction of acid esters of methylenebis(phosphonous acid) with carbonyl compounds

    International Nuclear Information System (INIS)

    Novikova, Z.S.; Odinets, I.L.; Lutsenko, I.F.

    1987-01-01

    The reaction of methylenebis(phosphonites) containing two hydrophosphoryl groupings with aliphatic and aromatic aldehydes and ketones in the presence of alkali metal fluorides leads to methylenebis(α-hydroxyalkylphosphinates). The reaction of methylenebis(phosphonites) containing one hydrophosphoryl groupings with carbonyl compounds in the presence of alkali metal fluorides proceeds with the formation of a new type of heterocyclic phosphorus compound, viz., 1,2λ 3 ,4λ 5 -oxadiphospholanes. The reaction of acid esters of methylenebis(phosphonous) acid with carbonyl compounds in the presence of alkali metal alkoxides or a tertiary amine is accompanied by phosphinate-phosphonate rearrangement of the intermediately formed α-hydroxylalkylphosphinates

  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. 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

  3. Metal phosphonate hybrid mesostructures: environmentally friendly multifunctional materials for clean energy and other applications.

    Science.gov (United States)

    Ma, Tian-Yi; Yuan, Zhong-Yong

    2011-10-17

    The synthesis of porous hybrid materials has been extended to mesoporous non-silica-based organic-inorganic hybrid materials, in which mesoporous metal phosphonates represent an important family. By using organically bridged polyphosphonic acids as coupling molecules, the homogeneous incorporation of a considerable number of organic functional groups into the metal phosphonate hybrid framework has been realized. Small amounts of organic additives and the pH value of the reaction solution have a large impact on the morphology and textural properties of the resultant hybrid mesoporous metal phosphonate solids. Cationic and nonionic surfactants can be used as templates for the synthesis of ordered mesoporous metal phosphonates. The materials are used as efficient adsorbents for heavy metal ions, CO₂, and aldehydes, as well as in the separation of polycyclic aromatic hydrocarbons. They are also useful photocatalysts under UV and simulated solar light irradiation for organic dye degradation. Further functionalization of the synthesized mesoporous hybrids makes them oxidation and acid catalysts, both with impressive performances in the fields of sustainable energy and environment. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Comparison of Zirconium Phosphonate-Modified Surfaces for Immobilizing Phosphopeptides and Phosphate-Tagged Proteins.

    Science.gov (United States)

    Forato, Florian; Liu, Hao; Benoit, Roland; Fayon, Franck; Charlier, Cathy; Fateh, Amina; Defontaine, Alain; Tellier, Charles; Talham, Daniel R; Queffélec, Clémence; Bujoli, Bruno

    2016-06-07

    Different routes for preparing zirconium phosphonate-modified surfaces for immobilizing biomolecular probes are compared. Two chemical-modification approaches were explored to form self-assembled monolayers on commercially available primary amine-functionalized slides, and the resulting surfaces were compared to well-characterized zirconium phosphonate monolayer-modified supports prepared using Langmuir-Blodgett methods. When using POCl3 as the amine phosphorylating agent followed by treatment with zirconyl chloride, the result was not a zirconium-phosphonate monolayer, as commonly assumed in the literature, but rather the process gives adsorbed zirconium oxide/hydroxide species and to a lower extent adsorbed zirconium phosphate and/or phosphonate. Reactions giving rise to these products were modeled in homogeneous-phase studies. Nevertheless, each of the three modified surfaces effectively immobilized phosphopeptides and phosphopeptide tags fused to an affinity protein. Unexpectedly, the zirconium oxide/hydroxide modified surface, formed by treating the amine-coated slides with POCl3/Zr(4+), afforded better immobilization of the peptides and proteins and efficient capture of their targets.

  5. Cu-Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

    NARCIS (Netherlands)

    Hornillos, Valentin; Perez, Manuel; Fananas-Mastral, Martin; Feringa, Ben L.

    An efficient and highly enantioselective copper-catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus-containing chiral

  6. Polysulfone Functionalized With Phosphonated Poly(pentafluorostyrene) Grafts for Potential Fuel Cell Applications

    DEFF Research Database (Denmark)

    Dimitrov, Ivaylo; Takamuku, Shogo; Jankova Atanasova, Katja

    2012-01-01

    A multi‐step synthetic strategy to polysulfone (PSU) grafted with phosphonated poly(pentafluorostyrene) (PFS) is developed. It involves controlled radical polymerization resulting in alkyne‐end functional PFS. The next step is the modification of PSU with a number of azide side groups. The grafting...

  7. Consensus pursuit of heterogeneous multi-agent systems under a directed acyclic graph

    Science.gov (United States)

    Yan, Jing; Guan, Xin-Ping; Luo, Xiao-Yuan

    2011-04-01

    This paper is concerned with the cooperative target pursuit problem by multiple agents based on directed acyclic graph. The target appears at a random location and moves only when sensed by the agents, and agents will pursue the target once they detect its existence. Since the ability of each agent may be different, we consider the heterogeneous multi-agent systems. According to the topology of the multi-agent systems, a novel consensus-based control law is proposed, where the target and agents are modeled as a leader and followers, respectively. Based on Mason's rule and signal flow graph analysis, the convergence conditions are provided to show that the agents can catch the target in a finite time. Finally, simulation studies are provided to verify the effectiveness of the proposed approach.

  8. A Directed Acyclic Graph-Large Margin Distribution Machine Model for Music Symbol Classification.

    Directory of Open Access Journals (Sweden)

    Cuihong Wen

    Full Text Available Optical Music Recognition (OMR has received increasing attention in recent years. In this paper, we propose a classifier based on a new method named Directed Acyclic Graph-Large margin Distribution Machine (DAG-LDM. The DAG-LDM is an improvement of the Large margin Distribution Machine (LDM, which is a binary classifier that optimizes the margin distribution by maximizing the margin mean and minimizing the margin variance simultaneously. We modify the LDM to the DAG-LDM to solve the multi-class music symbol classification problem. Tests are conducted on more than 10000 music symbol images, obtained from handwritten and printed images of music scores. The proposed method provides superior classification capability and achieves much higher classification accuracy than the state-of-the-art algorithms such as Support Vector Machines (SVMs and Neural Networks (NNs.

  9. A Directed Acyclic Graph-Large Margin Distribution Machine Model for Music Symbol Classification.

    Science.gov (United States)

    Wen, Cuihong; Zhang, Jing; Rebelo, Ana; Cheng, Fanyong

    2016-01-01

    Optical Music Recognition (OMR) has received increasing attention in recent years. In this paper, we propose a classifier based on a new method named Directed Acyclic Graph-Large margin Distribution Machine (DAG-LDM). The DAG-LDM is an improvement of the Large margin Distribution Machine (LDM), which is a binary classifier that optimizes the margin distribution by maximizing the margin mean and minimizing the margin variance simultaneously. We modify the LDM to the DAG-LDM to solve the multi-class music symbol classification problem. Tests are conducted on more than 10000 music symbol images, obtained from handwritten and printed images of music scores. The proposed method provides superior classification capability and achieves much higher classification accuracy than the state-of-the-art algorithms such as Support Vector Machines (SVMs) and Neural Networks (NNs).

  10. Polystyrene-Supported Acyclic Diaminocarbene Palladium Complexes in Sonogashira Cross-Coupling: Stability vs. Catalytic Activity

    Directory of Open Access Journals (Sweden)

    Vladimir N. Mikhaylov

    2018-04-01

    Full Text Available Two types of immobilized on the amino-functionalized polystyrene-supported acyclic diaminocarbene palladium complexes (ADC-PdII are investigated under Sonogashira cross-coupling conditions. Depending on substituents in the diaminocarbene fragment immobilized ADC-PdII, systems are found to have different catalytic activity and stability regarding Pd-leaching. PdII-diaminocarbenes possessing protons at both nitrogen atoms smoothly decompose into Pd0-containing species providing a catalytic “cocktail system” with high activity and ability to reuse within nine runs. Polymer-supported palladium (II complex bearing NBn–Ccarbene–NH-moiety exhibits greater stability while noticeably lower activity under Sonogashira cross-coupling. Four molecular ADC-PdII complexes are also synthesized and investigated with the aim of confirming proposed base-promoted pathway of ADC-PdII conversion through carbodiimide into an active Pd0 forms.

  11. Acid-Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release.

    Science.gov (United States)

    Mao, Dake; Liang, Yajun; Liu, Yamin; Zhou, Xianhao; Ma, Jiaqi; Jiang, Biao; Liu, Jia; Ma, Da

    2017-10-02

    Stimuli-responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition properties of CB[n]-type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Acyclic N-halamine-immobilized polyurethane: Preparation and antimicrobial and biofilm-controlling functions

    Science.gov (United States)

    Luo, Jie; Porteous, Nuala; Lin, Jiajin; Sun, Yuyu

    2015-01-01

    Hydroxyl groups were introduced onto polyurethane surfaces through 1,6-hexamethylene diisocyanate activation, followed by diethanolamine hydroxylation. Polymethacrylamide was covalently attached to the hydroxylated polyurethane through surface grafting polymerization of methacrylamide using cerium (IV) ammonium nitrate as an initiator. After bleach treatment, the amide groups of the covalently bound polymethacrylamide chains were transformed into N-halamines. The new N-halamine-immobilized polyurethane provided a total sacrifice of 107–108 colony forming units per milliliter of Staphylococcus aureus (Gram-positive bacteria), Escherichia coli (Gram-negative bacteria), and Candida albicans (fungi) within 10 min and successfully prevented bacterial and fungal biofilm formation. The antimicrobial and biofilm-controlling effects were both durable and rechargeable, pointing to great potentials of the new acyclic N-halamine-immobilized polyurethane for a broad range of related applications. PMID:26089593

  13. Molecular structure and conformation of two acyclic polythioethers: Implications for the design of heavy metal chelators

    Energy Technology Data Exchange (ETDEWEB)

    Desper, J.M.; Powell, D.R.; Gellman, S.H. (Univ. of Wisconsin, Madison (USA))

    1990-05-23

    The crystal structures of the 1,9-bis(p-tolyl)-2,5,8-trithianonane (1) and 1,12-bis(p-tolyl)-2,5,8,11-tetrathiadodecane (2) are reported. Previous studies of macrocyclic polythioethers have revealed a pronounced tendency for backbone CS-CC bonds to adopt gauche torsion angles. The same tendency is observed in the homologous acyclic polythioethers 1 and 2, demonstrating that the gauche preference is not simply the result of a macrocyclic constraint. Because of this gauche preference of CS-CC torsion units and the well-established anti preference of SC-CS torsion units, polythioethers constructed from ethylene sulfide subunits are generally far from preorganized for metal ion chelation.

  14. Theoretic derivation of directed acyclic subgraph algorithm and comparisons with message passing algorithm

    Science.gov (United States)

    Ha, Jeongmok; Jeong, Hong

    2016-07-01

    This study investigates the directed acyclic subgraph (DAS) algorithm, which is used to solve discrete labeling problems much more rapidly than other Markov-random-field-based inference methods but at a competitive accuracy. However, the mechanism by which the DAS algorithm simultaneously achieves competitive accuracy and fast execution speed, has not been elucidated by a theoretical derivation. We analyze the DAS algorithm by comparing it with a message passing algorithm. Graphical models, inference methods, and energy-minimization frameworks are compared between DAS and message passing algorithms. Moreover, the performances of DAS and other message passing methods [sum-product belief propagation (BP), max-product BP, and tree-reweighted message passing] are experimentally compared.

  15. Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study

    Science.gov (United States)

    Hicks, Jacqueline D.; Hyde, Alan M.; Cuezva, Alberto Martinez; Buchwald, Stephen L.

    2009-01-01

    We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups was found to be uniquely effective for this amidation. The critical aspects of the ligand were explored through synthetic, mechanistic, and computational studies. Systematic variation of the ligand revealed the importance of (1) a methoxy group on the aromatic carbon of the “top ring” ortho to the phosphorus and (2) two highly electron-withdrawing P-bound 3,5-(bis)trifluoromethylphenyl groups. Computational studies suggest the electron-deficient nature of the ligand is important in facilitating amide binding to the LPd(II)(Ph)(X) intermediate. PMID:19886610

  16. The effect of maturation on the configurations of acyclic isoprenoid acids in sediments

    Science.gov (United States)

    Mackenzie, A. S.; Patience, R. L.; Yon, D. A.; Maxwell, J. R.

    1982-05-01

    Within a variety of sedimentary rocks of differing maturity, the configurations of a suite of acyclic isoprenoid acids have been examined by gas Chromatographic (in a few cases also by combined gas chromatography-mass spectrometry) analysis of their diastereoisomeric methyl and (-)-menthyl esters. The samples include the Eocene Messel (Germany) and Green River (U.S.) shales, the Permian Irati shale (Brazil) and a number of Lower Toarcian shales from the Paris Basin. The isomer distributions show that isomerisation occurs at the chiral centres with increasing maturation (to increase the number of isomers) and that the rate of isomerisation increases for centres (C-2,C-3) closest to the carboxyl group. These results suggest that adsorption of the carboxyl group to a catalyst surface may control the isomerisation rates by way of access to the catalyst.

  17. Influence of Two Acyclic Homoterpenes (Tetranorterpenes) on the Foraging Behavior of Anthonomus grandis Boh.

    Science.gov (United States)

    Magalhães, D M; Borges, M; Laumann, R A; Woodcock, C M; Pickett, J A; Birkett, M A; Blassioli-Moraes, Maria Carolina

    2016-04-01

    Previous studies have shown that the boll weevil, Anthonomus grandis, is attracted to constitutive and conspecific herbivore-induced cotton volatiles, preferring the blend emitted by cotton at the reproductive over the vegetative stage. Moreover, this preference was paralleled by the release of the acyclic homoterpenes (tetranorterpenes) (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT) in Delta Opal cotton being higher at the vegetative than at the reproductive stage. Here, we evaluated whether this difference in release of acyclic homoterpenes also occurred in other cotton varieties, and if boll weevils could recognize these compounds as indicators of a specific cotton phenological stage. Results showed that cotton genotypes CNPA TB-90, BRS-293 and Delta Opal all produced higher levels of DMNT and TMTT at the vegetative stage than at the reproductive stage and that these homoterpenes allowed for principal component analysis separation of volatiles produced by the two phenological stages. Electroantennograms confirmed boll weevil antennal responses to DMNT and TMTT. Behavioral assays, using Y-tube olfactometers, showed that adding synthetic homoterpenes to reproductive cotton volatiles (mimicking cotton at the vegetative stage in terms of homoterpene levels) resulted in reduced attraction to boll weevils compared to that to unmodified reproductive cotton. Weevils showed no preference when given a choice between plants at the vegetative stage and the vegetative stage-mimicked plant. Altogether, the results show that DMNT and TMTT are used by boll weevils to distinguish between cotton phenological stages.

  18. New acyclic secondary metabolites from the biologically active fraction of Albizia lebbeck flowers.

    Science.gov (United States)

    Al-Massarani, Shaza M; El Gamal, Ali A; Abd El Halim, Mohamed F; Al-Said, Mansour S; Abdel-Kader, Maged S; Basudan, Omer A; Alqasoumi, Saleh I

    2017-01-01

    The total extract of Albizia lebbeck flowers was examined in vivo for its possible hepatoprotective activity in comparison with the standard drug silymarin at two doses. The higher dose expressed promising activity especially in reducing the levels of AST, ALT and bilirubin. Fractionation via liquid-liquid partition and reexamination of the fractions revealed that the n -butanol fraction was the best in improving liver biochemical parameters followed by the n -hexane fraction. However, serum lipid parameters were best improved with CHCl 3 fraction. The promising biological activity results initiated an intensive chromatographic purification of A. lebbeck flowers fractions. Two compounds were identified from natural source for the first time, the acyclic farnesyl sesquiterpene glycoside1-O-[6-O- α -l-arabinopyranosyl- β -d-glucopyranoside]-(2 E ,6 E -)-farnesol ( 6 ) and the squalene derivative 2,3-dihydroxy-2,3-dihydrosqualene ( 9 ), in addition to eight compounds reported here for the first time from the genus Albizia ; two benzyl glycosides, benzyl 1-O- β -d-glucopyranoside ( 1 ) and benzyl 6-O- α -l-arabinopyranosyl β -d-glucopyranoside ( 2 ); three acyclic monoterpene glycosides, linalyl β -d-glucopyranoside ( 3 ) and linalyl 6-O- α -l-arabinopyranosyl- β -d-glucopyranoside ( 4 ); (2 E )-3,7-dimethylocta-2,6-dienoate-6-O- α -l arabinopyranosyl- β -d-glucopyranoside ( 5 ), two oligoglycosides, n -hexyl- α -l arabinopyranosyl-(1 → 6)- β -d-glucopyranoside (creoside) ( 7 ) and n -octyl α -l-arabinopyranosyl-(1 → 6)- β -d-glucopyranoside (rhodiooctanoside) ( 8 ); and ethyl fructofuranoside ( 10 ). The structures of the isolated compounds were elucidated based on extensive examination of their spectroscopic 1D and 2D-NMR, MS, UV, and IR data. It is worth mentioning that, some of the isolated linalol glycoside derivatives were reported as aroma precursors.

  19. New acyclic secondary metabolites from the biologically active fraction of Albizia lebbeck flowers

    Directory of Open Access Journals (Sweden)

    Shaza M. Al-Massarani

    2017-01-01

    Full Text Available The total extract of Albizia lebbeck flowers was examined in vivo for its possible hepatoprotective activity in comparison with the standard drug silymarin at two doses. The higher dose expressed promising activity especially in reducing the levels of AST, ALT and bilirubin. Fractionation via liquid–liquid partition and reexamination of the fractions revealed that the n-butanol fraction was the best in improving liver biochemical parameters followed by the n-hexane fraction. However, serum lipid parameters were best improved with CHCl3 fraction. The promising biological activity results initiated an intensive chromatographic purification of A. lebbeck flowers fractions. Two compounds were identified from natural source for the first time, the acyclic farnesyl sesquiterpene glycoside1-O-[6-O-α-l-arabinopyranosyl-β-d-glucopyranoside]-(2E,6E--farnesol (6 and the squalene derivative 2,3-dihydroxy-2,3-dihydrosqualene (9, in addition to eight compounds reported here for the first time from the genus Albizia; two benzyl glycosides, benzyl 1-O-β-d-glucopyranoside (1 and benzyl 6-O-α-l-arabinopyranosyl β-d-glucopyranoside (2; three acyclic monoterpene glycosides, linalyl β-d-glucopyranoside (3 and linalyl 6-O-α-l-arabinopyranosyl-β-d-glucopyranoside (4; (2E-3,7-dimethylocta-2,6-dienoate-6-O-α-l arabinopyranosyl-β-d-glucopyranoside (5, two oligoglycosides, n-hexyl-α-l arabinopyranosyl-(1 → 6-β-d-glucopyranoside (creoside (7 and n-octyl α-l-arabinopyranosyl-(1 → 6-β-d-glucopyranoside (rhodiooctanoside (8; and ethyl fructofuranoside (10. The structures of the isolated compounds were elucidated based on extensive examination of their spectroscopic 1D and 2D-NMR, MS, UV, and IR data. It is worth mentioning that, some of the isolated linalol glycoside derivatives were reported as aroma precursors.

  20. Studies on the preparation and stability of samarium-153 propylene diamine tetramethylene phosphonate (PDTMP) complex as a bone seeker

    International Nuclear Information System (INIS)

    Majali, M.A.; Mathakar, A.R.; Shimpi, H.H.; Banerjee, Sharmila; Samuel, Grace

    2000-01-01

    Propylene diamine tetra methylene phosphonate (PDTMP) was synthesised by modifying a method reported for the synthesis of EDTMP. Complexation of the synthesised phosphonate ligand with 153 Sm was carried out by varying the experimental parameters and the complex was radiochemically characterized. Biodistribution studies showed that the uptake by bone in rats was 2% per g of bone, which was retained up to 48 h. The uptake by other organs was insignificant, except by the liver which showed a slightly higher absorption

  1. Synthesis and characterization of calcium hydroxy and fluoroapatite functionalized with methyl phosphonic dichloride

    Energy Technology Data Exchange (ETDEWEB)

    Agougui, Hassen; Aissa, Abdallah [Laboratoire de Physico-Chimie des Materiaux, Faculte des Sciences de Monastir, 5019 Monastir (Tunisia); Debbabi, Mongi, E-mail: m.debbabi@yahoo.fr [Laboratoire de Physico-Chimie des Materiaux, Faculte des Sciences de Monastir, 5019 Monastir (Tunisia)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer Surface reactivity of apatites toward methyl phosphonic dichloride is tested. Black-Right-Pointing-Pointer Chemical analysis shows that hydroxyapatite is more reactive. Black-Right-Pointing-Pointer NMR spectra show the formation of Ca-O-P{sub org} and P{sub inorg}-O-P{sub org} bonds. Black-Right-Pointing-Pointer AFM indicated that the texture surface was changed by grafting. - Abstract: The nature of apatite-organic molecule interaction was the subject of many investigations. Grafting the organic molecule onto the inorganic support may precede through either formation of covalent bonds or ionic interaction between superficial hydroxyl on the apatite surface and organic functions. The hybrid materials obtained by functionalization of apatite surfaces with phosphonate moieties are of interest for their potential applications such in catalysis, chromatography and biomedical domain. In this scope, calcium hydroxyl and fluoroapatite (CaHAp and CaFAp) were prepared in the presence of the methyl phosphonic dichloride (MPO), by contact method in organic solvent at 25 Degree-Sign C for 2 days. The products are rigorously characterized by chemical analysis, infrared (IR), MAS-NMR spectroscopies, powder X-ray diffraction (XRD), atomic force microscopy (AFM) and specific surface area (SSA). The X-ray powder analysis showed that the crystallinity was sensibly affected by the presence of organic moieties. The IR spectroscopy showed new vibration modes appearing related to phosphonate groups essentially at 2930, 1315, 945, 764 and 514 cm{sup -1}. The {sup 31}P MAS NMR spectrum for hydroxy and fluoroapatite exhibits a single signal at 2.8 ppm. After reaction with (MPO) the spectra show the presence of new signals, assigned to the formation of organic-inorganic bond between the superficial hydroxyl groups of the apatite ({identical_to}CaOH) and ({identical_to}POH) and methyl phosphonic dichloride. The SSA decreases with increasing

  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. Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

    Science.gov (United States)

    Kim, In-Hae; Park, Yong-Kyu; Nishiwaki, Hisashi; Hammock, Bruce D; Nishi, Kosuke

    2015-11-15

    Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as a secondary pharmacophore. A tert-butyl group (16) on the alpha carbon was found to yield most potent inhibition on the target enzyme. A 4-50-fold drop in inhibition was induced by other substituents such as aryls, substituted aryls, cycloalkyls, and alkyls. Then, the modification of the O-substituents on the phosphonate function revealed that diethyl groups (16 and 23) were preferable for inhibition to other longer alkyls or substituted alkyls. In amide compounds with the optimized diethylphosphonate moiety and an alkyl substitution such as adamantane (16), tetrahydronaphthalene (31), or adamantanemethane (36), highly potent inhibitions were gained. In addition, the resulting potent amide-phosphonate compounds had reasonable water solubility, suggesting that substituted phosphonates in amide inhibitors are effective for both inhibition potency on the human sEH and water solubility as a secondary pharmacophore. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. High temperature proton exchange membranes prepared from epoxycyclohexylethyltrimethoxysilane and amino trimethylene phosphonic acid as anhydrous proton conductors

    International Nuclear Information System (INIS)

    Chen, Cheng; Shen, Chunhui; Kong, Gengjin; Gao, Shanjun

    2013-01-01

    High temperature anhydrous proton exchange membranes based on phosphonic acid were prepared from epoxycyclohexylethyltrimethoxysilane (EHTMS) and amino trimethylene phosphonic acid (ATMP) by sol–gel process. The structures and properties of membranes with different phosphonic acid content were extensively characterized by FTIR, TG-DSC and XRD. Their proton conductivity under dry condition was also investigated under different temperature. The results show that the proton conductivity of the prepared membranes strongly depends on temperature, and the proton conductivity ranges from 8.81 × 10 −5 S cm −1 at 20 °C to 4.65 × 10 −2 S cm −1 at 140 °C under anhydrous condition. It indicates that the increasing temperature is favorable for congregating of the grafted–PO 3 H 2 and increasing of the proton mobility. In addition, from the results of AFM images, it was confirmed that the continuous distribution of phosphonic acid groups is favorable for the formation of the proton transport channel, which can significantly enhance the proton conductivity of the membranes. Highlights: ► Hybrid membranes of Epoxycyclohexylethyltrimethoxysilane and Amino trimethylene phosphonic acid. ► The proton conductivity is 4.65 × 10 −2 S cm −1 at 140 °C under anhydrous condition. ► Continuous uniform distributions of phosphonic acid groups can be observed by AFM. ► There could be hydrogen bond network within high temperature membranes

  5. 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

  6. 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.

  7. 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...

  8. 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

  9. Synthesis of phosphonic acid derivatized bipyridine ligands and their ruthenium complexes.

    Science.gov (United States)

    Norris, Michael R; Concepcion, Javier J; Glasson, Christopher R K; Fang, Zhen; Lapides, Alexander M; Ashford, Dennis L; Templeton, Joseph L; Meyer, Thomas J

    2013-11-04

    Water-stable, surface-bound chromophores, catalysts, and assemblies are an essential element in dye-sensitized photoelectrosynthesis cells for the generation of solar fuels by water splitting and CO2 reduction to CO, other oxygenates, or hydrocarbons. Phosphonic acid derivatives provide a basis for stable chemical binding on metal oxide surfaces. We report here the efficient synthesis of 4,4'-bis(diethylphosphonomethyl)-2,2'-bipyridine and 4,4'-bis(diethylphosphonate)-2,2'-bipyridine, as well as the mono-, bis-, and tris-substituted ruthenium complexes, [Ru(bpy)2(Pbpy)](2+), [Ru(bpy)(Pbpy)2](2+), [Ru(Pbpy)3](2+), [Ru(bpy)2(CPbpy)](2+), [Ru(bpy)(CPbpy)2](2+), and [Ru(CPbpy)3](2+) [bpy = 2,2'-bipyridine; Pbpy = 4,4'-bis(phosphonic acid)-2,2'-bipyridine; CPbpy = 4,4'-bis(methylphosphonic acid)-2,2'-bipyridine].

  10. A Pyrene- and Phosphonate-Containing Fluorescent Probe as Guest Molecule in a Host Polymer Matrix

    Directory of Open Access Journals (Sweden)

    Jacqueline Marchand-Brynaert

    2013-02-01

    Full Text Available New host-guest materials have been prepared by incorporation of a home-made organic probe displaying a pyrene motif and a phosphonate function into a regular amphiphilic copolymer. Using powder X-Ray diffraction, photoluminescence and FT-IR spectroscopy, we have been able to study the non-covalent interactions between the host matrix and the guest molecule in the solid state. Interestingly, we have shown that the matrix directs the guest spatial localization and alters its properties. Thanks to the comparison of pyrene vs. N-pyrenylmaleimide derivatives, the influence of the chemical nature of the guest molecules on the non-covalent interactions with the host have been studied. In addition, using polyethylene glycol as a reference host, we have been able to evidence a true matrix effect within our new insertion materials. The phosphonated guest molecule appears to be a novel probe targeting the hydrophilic domain of the host copolymer.

  11. Exploiting the high-affinity phosphonate-hydroxyapatite nanoparticle interaction for delivery of radiation and drugs

    International Nuclear Information System (INIS)

    Ong, Hooi Tin; Loo, Joachim S. C.; Boey, Freddy Y. C.; Russell, Stephen J.; Ma Jan; Peng, Kah-Whye

    2008-01-01

    Hydroxyapatite is biocompatible and used in various biomedical applications. Here, we generated hydroxyapatite nanoparticles (HNPs) of various sizes (40-200 nm) and demonstrated that they can be stably loaded with drugs or radioisotopes by exploiting the high-affinity HA-(poly)phosphonate interaction. Clinically available phosphonates, clodronate, and Tc-99m-methylene-diphosphonate (Tc-99m-MDP), were efficiently loaded onto HNPs within 15 min. Biodistribution of radiolabeled HNP-MDP-Tc99m in mice was monitored non-invasively using microSPECT-CT. Imaging and dosimetry studies indicated that the HNPs, regardless of size, were quickly taken up by Kupffer cells in the liver after systemic administration into mice. Clodronate loaded onto HNPs remained biologically active and were able to result in selective depletion of Kupffer cells. This method of drug or isotope loading on HA is fast and easy as it eliminates the need for additional surface modifications of the nanoparticles

  12. 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.

  13. 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.

  14. Investigating temporary acyclicity in a captive group of Asian elephants (Elephas maximus): Relationship between management, adrenal activity and social factors.

    Science.gov (United States)

    Edwards, Katie L; Trotter, Jessica; Jones, Martin; Brown, Janine L; Steinmetz, Hanspeter W; Walker, Susan L

    2016-01-01

    Routine faecal steroid monitoring has been used to aid the management of five captive Asian elephant (Elephas maximus) females at Chester Zoo, UK, since 2007. Progestagen analysis initially revealed synchronised oestrous cycles among all females. However, a 14- to 20-week period of temporary acyclicity subsequently occurred in three females, following several management changes (increased training, foot-care and intermittent matriarch removal for health reasons) and the initiation of pregnancy in another female. The aim of this study was to retrospectively investigate whether these management changes were related to increased adrenal activity and disruption of ovarian activity, or whether social factors may have been involved in the temporary cessation of cyclicity. Faecal samples collected every other day were analysed to investigate whether glucocorticoid metabolites were related to reproductive status (pregnant, cycling, acyclic) or management (training, foot-care, matriarch presence). Routine training and foot-care were not associated with adrenal activity; however, intensive foot-care to treat an abscess in one female was associated with increased glucocorticoid concentration. Matriarch presence influenced adrenal activity in three females, being lower when the matriarch was separated from the group at night compared to being always present. However, in the females that exhibited temporary acyclicity, there was no consistent relationship between glucocorticoids and cyclicity state. Although the results of this study do not fully explain this occurrence, the highly synchronised nature of oestrous cycles within this group, and the concurrent acyclicity in three females, raises the question of whether social factors could have been involved in the temporary disruption of ovarian activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Geminal difunctionalization of α-diazo arylmethylphosphonates: synthesis of fluorinated phosphonates.

    Science.gov (United States)

    Zhou, Yujing; Zhang, Yan; Wang, Jianbo

    2016-11-08

    A general approach towards diverse fluorinated phosphonates via geminal difunctionalization reactions of α-diazo arylmethylphosphonates is described. The diazo functionality (RR'C[double bond, length as m-dash]N 2 ) is successfully converted to RR'CF 2 , RR'CHF, RR'CFBr or RR'CFNR'' 2 groups by employing different fluorination reagents. A variety of fluorinated organophosphorus compounds were readily accessed in good to excellent yields from a common type of precursor.

  16. Preparation and use of crystalline bis-monoorganic phosphonate and phosphate salts of tetravalent metals

    Science.gov (United States)

    Maya, L.

    1980-06-26

    A method of preparing and using the crystalline organic derivatives of the tetravalent metal phosphates and phosphonates provides for the contacting of an aqueous solution of a metal nitrate, with a solution of an organophosphorus acid for a period of time at room temperature that is sufficient for the formation of a metal phosphate product, and thereafter recovering said product. According to the invention, the product of the disclosed process is used in effecting analytical separations, such as ion exchange and chromatography.

  17. Synthesis and Functionalization of Poly(ethylene oxide-b-ethyloxazoline) Diblock Copolymers with Phosphonate Ions

    OpenAIRE

    Chen, Alfred Yuen-Wei

    2013-01-01

    Poly(ethylene oxide) (PEO) and poly(2-ethyl-2-oxazoline) (PEOX) are biocompatible polymers that act as hydrophilic "stealth" drug carriers. As block copolymers, the PEOX group offers a wider variety of functionalization. The goal of this project was to synthesize a poly(ethylene oxide)-b-poly(2-ethyl-2-oxazoline) (PEO-b-PEOX) block copolymer and functionalize pendent groups of PEOX with phosphonic acid. This was achieved through cationic ring opening polymerization (CROP) of 2-...

  18. Enzymatic study on AtCCD4 and AtCCD7 and their potential to form acyclic regulatory metabolites

    KAUST Repository

    Bruno, Mark

    2016-09-29

    The Arabidopsis carotenoid cleavage dioxygenase 4 (AtCCD4) is a negative regulator of the carotenoid content of seeds and has recently been suggested as a candidate for the generation of retrograde signals that are thought to derive from the cleavage of poly-cis-configured carotene desaturation intermediates. In this work, we investigated the activity of AtCCD4 in vitro and used dynamic modeling to determine its substrate preference. Our results document strict regional specificity for cleavage at the C9–C10 double bond in carotenoids and apocarotenoids, with preference for carotenoid substrates and an obstructing effect on hydroxyl functions, and demonstrate the specificity for all-trans-configured carotenes and xanthophylls. AtCCD4 cleaved substrates with at least one ionone ring and did not convert acyclic carotene desaturation intermediates, independent of their isomeric states. These results do not support a direct involvement of AtCCD4 in generating the supposed regulatory metabolites. In contrast, the strigolactone biosynthetic enzyme AtCCD7 converted 9-cis-configured acyclic carotenes, such as 9-cis-ζ-carotene, 9\\'-cis-neurosporene, and 9-cis-lycopene, yielding 9-cis-configured products and indicating that AtCCD7, rather than AtCCD4, is the candidate for forming acyclic retrograde signals.

  19. Enzymatic study on AtCCD4 and AtCCD7 and their potential to form acyclic regulatory metabolites

    KAUST Repository

    Bruno, Mark; Koschmieder, Julian; Wuest, Florian; Schaub, Patrick; Fehling-Kaschek, Mirjam; Timmer, Jens; Beyer, Peter; Al-Babili, Salim

    2016-01-01

    The Arabidopsis carotenoid cleavage dioxygenase 4 (AtCCD4) is a negative regulator of the carotenoid content of seeds and has recently been suggested as a candidate for the generation of retrograde signals that are thought to derive from the cleavage of poly-cis-configured carotene desaturation intermediates. In this work, we investigated the activity of AtCCD4 in vitro and used dynamic modeling to determine its substrate preference. Our results document strict regional specificity for cleavage at the C9–C10 double bond in carotenoids and apocarotenoids, with preference for carotenoid substrates and an obstructing effect on hydroxyl functions, and demonstrate the specificity for all-trans-configured carotenes and xanthophylls. AtCCD4 cleaved substrates with at least one ionone ring and did not convert acyclic carotene desaturation intermediates, independent of their isomeric states. These results do not support a direct involvement of AtCCD4 in generating the supposed regulatory metabolites. In contrast, the strigolactone biosynthetic enzyme AtCCD7 converted 9-cis-configured acyclic carotenes, such as 9-cis-ζ-carotene, 9'-cis-neurosporene, and 9-cis-lycopene, yielding 9-cis-configured products and indicating that AtCCD7, rather than AtCCD4, is the candidate for forming acyclic retrograde signals.

  20. Enzymatic study on AtCCD4 and AtCCD7 and their potential to form acyclic regulatory metabolites

    Science.gov (United States)

    Bruno, Mark; Koschmieder, Julian; Wuest, Florian; Schaub, Patrick; Fehling-Kaschek, Mirjam; Timmer, Jens; Beyer, Peter; Al-Babili, Salim

    2016-01-01

    The Arabidopsis carotenoid cleavage dioxygenase 4 (AtCCD4) is a negative regulator of the carotenoid content of seeds and has recently been suggested as a candidate for the generation of retrograde signals that are thought to derive from the cleavage of poly-cis-configured carotene desaturation intermediates. In this work, we investigated the activity of AtCCD4 in vitro and used dynamic modeling to determine its substrate preference. Our results document strict regional specificity for cleavage at the C9–C10 double bond in carotenoids and apocarotenoids, with preference for carotenoid substrates and an obstructing effect on hydroxyl functions, and demonstrate the specificity for all-trans-configured carotenes and xanthophylls. AtCCD4 cleaved substrates with at least one ionone ring and did not convert acyclic carotene desaturation intermediates, independent of their isomeric states. These results do not support a direct involvement of AtCCD4 in generating the supposed regulatory metabolites. In contrast, the strigolactone biosynthetic enzyme AtCCD7 converted 9-cis-configured acyclic carotenes, such as 9-cis-ζ-carotene, 9'-cis-neurosporene, and 9-cis-lycopene, yielding 9-cis-configured products and indicating that AtCCD7, rather than AtCCD4, is the candidate for forming acyclic retrograde signals. PMID:27811075

  1. Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties

    Directory of Open Access Journals (Sweden)

    Sachin D. Padghan

    2017-08-01

    Full Text Available A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE properties in water/acetonitrile (ACN solutions. Dynamic light scattering (DLS characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe3+ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe3+ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe3+ complex showed a reversible UV-vis response in the presence of EDTA.

  2. Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

    Science.gov (United States)

    Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

    2011-01-01

    A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

  3. Directed acyclic graphs (DAGs): an aid to assess confounding in dental research.

    Science.gov (United States)

    Merchant, Anwar T; Pitiphat, Waranuch

    2002-12-01

    Confounding, a special type of bias, occurs when an extraneous factor is associated with the exposure and independently affects the outcome. In order to get an unbiased estimate of the exposure-outcome relationship, we need to identify potential confounders, collect information on them, design appropriate studies, and adjust for confounding in data analysis. However, it is not always clear which variables to collect information on and adjust for in the analyses. Inappropriate adjustment for confounding can even introduce bias where none existed. Directed acyclic graphs (DAGs) provide a method to select potential confounders and minimize bias in the design and analysis of epidemiological studies. DAGs have been used extensively in expert systems and robotics. Robins (1987) introduced the application of DAGs in epidemiology to overcome shortcomings of traditional methods to control for confounding, especially as they related to unmeasured confounding. DAGs provide a quick and visual way to assess confounding without making parametric assumptions. We introduce DAGs, starting with definitions and rules for basic manipulation, stressing more on applications than theory. We then demonstrate their application in the control of confounding through examples of observational and cross-sectional epidemiological studies.

  4. Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro

    Directory of Open Access Journals (Sweden)

    Kazuhisa Murai

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC frequently develops from hepatitis C virus (HCV and hepatitis B virus (HBV infection. We previously reported that peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity. Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA, and all-trans-retinoic acid (ATRA, had no effect or rather increased HBV replication. Mechanistically, although peretinoin increased the expression of HBV-related transcription factors, as observed for other retinoids, peretinoin enhanced the binding of histone deacetylase 1 (HDAC1 to cccDNA in the nucleus and negatively regulated HBV transcription. Moreover, peretinoin significantly inhibited the expression of SPHK1, a potential inhibitor of HDAC activity, and might be involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in cells cancelled the inhibition of HBV replication induced by peretinoin. This indicates that peretinoin activates HDAC1 and thereby suppresses HBV replication by inhibiting the sphingosine metabolic pathway. Therefore, peretinoin may be a novel therapeutic agent for HBV replication and chemoprevention against HCC.

  5. A novel 13 residue acyclic peptide from the marine snail, Conus monile, targets potassium channels.

    Science.gov (United States)

    Sudarslal, Sadasivannair; Singaravadivelan, Govindaswamy; Ramasamy, Palanisamy; Ananda, Kuppanna; Sarma, Siddhartha P; Sikdar, Sujit K; Krishnan, K S; Balaram, Padmanabhan

    2004-05-07

    A novel 13-residue peptide Mo1659 has been isolated from the venom of a vermivorous cone snail, Conus monile. HPLC fractions of the venom extract yielded an intense UV absorbing fraction with a mass of 1659Da. De novo sequencing using both matrix assisted laser desorption and ionization and electrospray MS/MS methods together with analysis of proteolytic fragments successfully yielded the amino acid sequence, FHGGSWYRFPWGY-NH(2). This was further confirmed by comparison with the chemically synthesized peptide and by conventional Edman sequencing. Mo1659 has an unusual sequence with a preponderance of aromatic residues and the absence of apolar, aliphatic residues like Ala, Val, Leu, and Ile. Mo1659 has no disulfide bridges distinguishing it from the conotoxins and bears no sequence similarity with any of the acyclic peptides isolated thus far from the venom of cone snails. Electrophysiological studies on the effect of Mo1659 on measured currents in dorsal root ganglion neurons suggest that the peptide targets non-inactivating voltage-dependent potassium channels.

  6. Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats.

    Science.gov (United States)

    Colli, Vilma Clemi; Okamoto, Roberta; Spritzer, Poli Mara; Dornelles, Rita Cássia Menegati

    2012-09-01

    OT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats. Females Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12h apart) injections of saline (NaCl 0.15M - control group) or OT (45μg/rat - treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration). Calcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes. OT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process. Published by Elsevier Ltd.

  7. Bifurcatriol, a New Antiprotozoal Acyclic Diterpene from the Brown Alga Bifurcaria bifurcata

    Directory of Open Access Journals (Sweden)

    Vangelis Smyrniotopoulos

    2017-08-01

    Full Text Available Linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. This study reports bifurcatriol (1, a new linear diterpene featuring two stereogenic centers isolated from the Irish brown alga Bifurcaria bifurcata. The gross structure of this new natural product was elucidated based on its spectroscopic data (IR, 1D and 2D-NMR, HRMS. Its absolute configuration was identified by experimental and computational vibrational circular dichroism (VCD spectroscopy, combined with the calculation of 13C-NMR chemical shielding constants. Bifurcatriol (1 was tested for in vitro antiprotozoal activity towards a small panel of parasites (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, and Leishmania donovani and cytotoxicity against mammalian primary cells. The highest activity was exerted against the malaria parasite P. falciparum (IC50 value 0.65 μg/mL with low cytotoxicity (IC50 value 56.6 μg/mL. To our knowledge, this is the first successful application of VCD and DP4 probability analysis of the calculated 13C-NMR chemical shifts for the simultaneous assignment of the absolute configuration of multiple stereogenic centers in a long-chain acyclic natural product.

  8. Synthesis of modified cyclic and acyclic dextrins and comparison of their complexation ability

    Directory of Open Access Journals (Sweden)

    Kata Tuza

    2014-12-01

    Full Text Available We compared the complex forming ability of α-, β- and γ-cyclodextrins (α-CD, β-CD and γ-CD with their open ring analogs. In addition to the native cyclodextrins also modified cyclodextrins and the corresponding maltooligomers, functionalized with neutral 2-hydroxypropyl moieties, were synthesized. A new synthetic route was worked out via bromination, benzylation, deacetylation and debenzylation to obtain the 2-hydroxypropyl maltooligomer counterparts. The complexation properties of non-modified and modified cyclic and acyclic dextrins were studied and compared by photon correlation spectroscopy (PCS and capillary electrophoresis (CE using model guest compounds. In some cases cyclodextrins and their open-ring analogs (acyclodextrins show similar complexation abilities, while with other guests considerably different behavior was observed depending on the molecular dimensions and chemical characteristics of the guests. This was explained by the enhanced flexibility of the non-closed rings. Even the signs of enantiorecognition were observed for the chloropheniramine/hydroxypropyl maltohexaose system. Further studies are planned to help the deeper understanding of the interactions.

  9. Optimal allocation of multi-state retransmitters in acyclic transmission networks

    International Nuclear Information System (INIS)

    Levitin, Gregory

    2002-01-01

    In this paper, an algorithm for optimal allocation of multi-state elements (MEs) in acyclic transmission networks (ATNs) is suggested. The ATNs consist of a number of positions (nodes) in which MEs capable of receiving and sending a signal are allocated. Each network has a root position where the signal source is located, a number of leaf positions that can only receive a signal, and a number of intermediate positions containing MEs capable of transmitting the received signal to some other nodes. Each ME that is located in a nonleaf node can have different states determined by a set of nodes receiving the signal directly from this ME. The probability of each state is assumed to be known for each ME. The ATN reliability is defined as the probability that a signal from the root node is transmitted to each leaf node. The optimal distribution of MEs with different characteristics among ATN positions provides the greatest possible ATN reliability. The suggested algorithm is based on using a universal generating function technique for network reliability evaluation. A genetic algorithm is used as the optimization tool. Illustrative examples are presented

  10. Maximizing survivability of acyclic transmission networks with multi-state retransmitters and vulnerable nodes

    International Nuclear Information System (INIS)

    Levitin, Gregory

    2002-01-01

    In this paper, an algorithm for optimal allocation of multi-state elements (MEs) in acyclic transmission networks (ATNs) with vulnerable nodes is suggested. The ATNs consist of a number of positions (nodes) in which MEs capable of receiving and sending a signal are allocated. Each network has a root position where the signal source is located, a number of leaf positions that can only receive a signal, and a number of intermediate positions containing MEs capable of transmitting the received signal to some other nodes. Each ME that is located in a nonleaf node can have different states determined by a set of nodes receiving the signal directly from this ME. The probability of each state is assumed to be known for each ME. Each ATN node with all the MEs allocated at this node can be destroyed by external impact (common cause failure) with a given probability. The ATN survivability is defined as the probability that a signal from the root node is transmitted to each leaf node. The optimal distribution of MEs with different characteristics among ATN positions provides the greatest possible ATN survivability. It is shown that the node vulnerability index affects the optimal distribution. The suggested algorithm is based on using a universal generating function technique for network survivability evaluation. A genetic algorithm is used as the optimization tool. Illustrative examples are presented

  11. Executive Summary of Ares V: Lunar Capabilities Concept Review Through Phase A-Cycle 3

    Science.gov (United States)

    Holladay, J. B.; Baggett, K. E.; Feldman, S. M.

    2011-01-01

    This Technical Memorandum (TM) was generated as an overall Ares V summary from the Lunar Capabilities Concept Review (LCCR) through Phase A-Cycle 3 (PA-C3) with the intent that it may be coupled with separately published appendices for a more detailed, integrated narrative. The Ares V has evolved from the initial point of departure (POD) 51.00.48 LCCR configuration to the current candidate POD, PA-C3D, and the family of vehicles concept that contains vehicles PA-C3A through H. The logical progression from concept to POD vehicles is summarized in this TM and captures the trade space and performance of each. The family-of-vehicles concept was assessed during PA-C3 and offered flexibility in the path forward with the ability to add options deemed appropriate. A description of each trade space is given in addition to a summary of each Ares V element. The Ares V contributions to a Mars campaign are also highlighted with the goal of introducing Ares V capabilities within the trade space. The assessment of the Ares V vehicle as it pertains to Mars missions remained locked to the architecture presented in Mars Design Reference Authorization 5.0 using the PA-C3D vehicle configuration to assess Mars transfer vehicle options, in-space EDS capabilities, docking adaptor and propellant transfer assessments, and lunar and Mars synergistic potential.

  12. Removal of phosphonates from industrial wastewater with UV/FeII, Fenton and UV/Fenton treatment.

    Science.gov (United States)

    Rott, Eduard; Minke, Ralf; Bali, Ulusoy; Steinmetz, Heidrun

    2017-10-01

    Phosphonates are an important group of phosphorus-containing compounds due to their increasing industrial use and possible eutrophication potential. This study involves investigations into the methods UV/Fe II , Fenton and UV/Fenton for their removal from a pure water matrix and industrial wastewaters. It could be shown that the degradability of phosphonates by UV/Fe II (6 kWh/m 3 ) in pure water crucially depended on the pH and was higher the less phosphonate groups a phosphonate contains. The UV/Fe II method is recommended in particular for the treatment of concentrates with nitrogen-free phosphonates, only little turbidity and a low content of organic compounds. Using Fenton reagent, the degradation of polyphosphonates was relatively weak in a pure water matrix (Fenton method (6 kWh/m 3 ), those phosphonates with the smallest numbers of phosphonate groups were easier degraded as well at pH 3.5 in a pure water matrix (o-PO 4 3- formation rates of up to 80%). Despite an incomplete transformation of organically bound phosphorus to o-PO 4 3- with Fenton reagent in an organically highly polluted wastewater (max. 15%), an almost total removal of the total P occurred. The most efficient total P elimination rates were achieved in accordance with the following Fenton implementation: reaction → sludge separation (acidic) → neutralization of the supernatant → sludge separation (neutral). Accordingly, a neutralization directly after the reaction phase led to a lower total P removal extent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Highly stable acyclic bifunctional chelator for {sup 64}Cu PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Abada, S.; Lecointre, A.; Christine, C.; Charbonniere, L. [CNRS/UDS, EPCM, Strasbourg (France). Lab. d' Ingenierie Appliquee a l' Analyse; Dechamps-Olivier, I. [Univ. de Reims Champagne Ardenne, Reims (France). Group Chimie de Coordination; Platas-Iglesias, C. [Univ. da Coruna (Spain). Dept. de Quimica Fundamental; Elhabiri, M. [CNRS/UDS, EPCM, Strasbourg (France). Lab. de Physico-Chimie Bioinorganique

    2011-07-01

    Ligand L{sup 1}, based on a pyridine scaffold, functionalized by two bis(methane phosphonate)aminomethyl groups, was shown to display a very high affinity towards Cu(II) (log K{sub CuL}=22.7) and selectivity over Ni(II), Co(II), Zn(II) and Ga(III) ({delta} log K{sub ML}>4) as shown by the values of the stability constants obtained from potentiometric measurements. Insights into the coordination mode of the ligand around Cu(II) cation were obtained by UV-Vis absorption and EPR spectroscopies as well as density functional theory (DFT) calculations (B3LYP model) performed in aqueous solution. The results point to a pentacoordination pattern of the metal ion in the fully deprotonated [CuL{sup 1}]{sup 6-} species. Considering the beneficial thermodynamic parameters of this ligand, kinetic experiments were run to follow the formation of the copper(II) complexes, indicating a very rapid formation of the complex, appropriate for {sup 64}Cu complexation. As L{sup 1} represents a particularly interesting target within the frame of {sup 64}Cu PET imaging, a synthetic protocol was developed to introduce a labeling function on the pyridyl moiety of L{sup 1}, thereby affording L{sup 2}, a potential bifunctional chelator (BFC) for PET imaging.

  14. 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...

  15. Catalytic phosphonation of high performance polymers and POSS. Novel components for polymer blend and nanocomposite fuel cell membranes

    Energy Technology Data Exchange (ETDEWEB)

    Bock, T.R.

    2006-10-15

    Aim of this thesis was the preparation and evaluation of phosphonated high performance (HP) polyelectrolytes and polyhedral oligomeric silsesquioxanes (POSS) for polyelectrolyte membrane fuel cell (PEMFC) application. Brominated derivatives of the commercial high performance (HP) polymers poly(ethersulfone) (PES), poly(etheretherketone) (PEEK), poly(phenylsulfone) (PPSu), poly(sulfone) (PSU) and of octaphenyl-POSS of own production were phosphonated by Ni-catalysed Arbuzov reaction. Phosphonated PSU was cast into pure and blend films with sulfonated PEEK (s-PEEK) to investigate H+-conductivity, water uptake and film morphology. Blend films' properties were referenced to films containing unmodified blend partners. Solution-compounding of phosphonated octaphenyl-POSS and s-PEEK was used to produce novel nanocomposite films. An in-situ zirconisation method was assessed as convenient strategy for novel ionically crosslinked membranes of enhanced swelling resistance. Dibromo isocyanuric acid (DBI) and N-bromo succinimide (NBS) as brominating agents allowed polymer analogous preparation of the novel brominated PES and PEEK with precise reaction control. A random distribution of functional groups, i.e. polyelectrolytes' microstructural homogeneity was revealed as decisive factor concerning solubility of phosphonated PSU. Brominated phT8 was prepared with Br2 by a high temperature approach in tetrachloroethane (TCE). Brominated polymers were phosphonated by Ni-catalysis in non-coordinating high temperature solvents, such as diphenylether, benzophenone and diphenylsulfone without notable solvent influence. The lack of solvent - catalyst complexes and high reaction temperatures of 180-200 C led to halogen-free phosphonates with unprecedented high functionalities. Polymer analogous application of P(OSiMe3)3 offered a novel direct access to easily cleavable disilyl ester derivatives. These were obtained from PEEK and PSU in near quantitative yields at NiCl2-loads as

  16. 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…

  17. 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

  18. 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.

  19. 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...

  20. 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)

  1. Hydrothermal synthesis, crystal structure and properties of a novel chain coordination polymer constructed by tetrafunctional phosphonate anions and cobalt ions

    International Nuclear Information System (INIS)

    Guan, Lei; Wang, Ying

    2015-01-01

    A novel cobalt phosphonate, [Co(HL)(H 2 O) 3 ] n (1) (L=N(CH 2 PO 3 H) 3 3− ) has been synthesized by hydrothermal reaction at 150 °C and structurally characterized by X-ray diffraction, infrared spectroscopy, elemental and thermogravimetric analysis. Complex 1 features a 1D chain structure with double-channel built from CoO 6 octahedra bridged together by the phosphonate groups. Each cobalt ion is octahedrally coordinated by three phosphonate oxygen atoms and three water molecules. The coordinated water molecules can form the hydrogen bonds with the phosphonate oxygen atoms to link the 1D chains, building a 2D layered structure, further resulting in a 3D network. The luminescence spectrum indicates an emission maximum at 435 nm. The magnetic susceptibility curve exhibits a dominant antiferromagnetic behavior with a weakly ferromagnetic component at low temperatures. - Graphical abstract: The connectivity between cobalt ions and the ligands results in a chain structure with a 1D double-channel structure, which is constructed by A-type subrings and B-type subrings. - Highlights: • The tetrafunctional phosphonate ligand was used as the ligand. • A novel chain structure can be formed by A-type rings and B-type rings. • Two types of rings can form a 1D double-channel structure, along the c-axis

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Interest of bone scintigraphy in the care of maxillary osteo-necroses induced by bis-phosphonates

    International Nuclear Information System (INIS)

    Agossa, Kevimy

    2012-01-01

    First cases of bis-phosphonates related osteonecrosis of jaws (BRONJ) have been described in 2003. Since then, this subject is one of the central concerns of several scientific communities, well beyond the oral sphere. The prevalence of BRONJ is evolving. Their etiology is not well established and the results of the treatments are inconstant. So many points that make the care to patients under bis-phosphonates really complex. Early diagnosis is essential in treatment outcome. So nuclear imaging including scintigraphy with technetium 99m seems to be helpful. It may allow detection before the onset of symptoms, facilitate localization of necrosis and it may be useful for the monitoring of such lesions after surgery. These are new applications for oncologist and dentist, in order to improve the management of patients treated by bis-phosphonates. (author) [fr

  8. Bis-phosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, M.; Lecercle, D.; Taran, F. [CEA Saclay, IBiTecS, Serv Chim Bioorgan et Marquage, F-91191 Gif Sur Yvette (France); Grillon, G.; Le Gall, B.; Serandour, A.L.; Poncy, J.L. [CEA, DSV, DRR, Lab Radiotoxicol, F-91680 Bruyeres Le Chatel (France); Bailly, T.; Burgada, R.; Lecouvey, M.; Challeix, V. [CNRS, Lab Chim Struct Biomol, UMR 7033, F-93017 Bobigny (France); Leydier, A.; Pellet-Rostaing, S. [Univ Lyon 1, ICBMS, UMR 5246, Lab Catalyse et Synth Organ, F-69622 Villeurbanne (France); Ansoborlo, E. [CEA, DEN, DRCP, CETAMA, VRH Marcoule, F-30207 Bagnols Sur Ceze (France)

    2008-07-01

    A library of bis-phosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromo-phoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bis-phosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bis-phosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal. (authors)

  9. Hydrothermal synthesis for new multifunctional materials: A few examples of phosphates and phosphonate-based hybrid materials

    Energy Technology Data Exchange (ETDEWEB)

    Rueff, Jean-Michel, E-mail: jean-michel.rueff@ensicaen.fr [Laboratoire CRISMAT, CNRS UMR 6508, ENSICAEN, 6 bd du Maréchal Juin, F-14050 Caen Cedex (France); Poienar, Maria [National Institute for Research and Development in Electrochemistry and Condensed Matter, Plautius Andronescu Str Nr. 1, 300224 Timisoara (Romania); Guesdon, Anne; Martin, Christine; Maignan, Antoine [Laboratoire CRISMAT, CNRS UMR 6508, ENSICAEN, 6 bd du Maréchal Juin, F-14050 Caen Cedex (France); Jaffrès, Paul-Alain [Université de Brest, Université Européenne de Bretagne, CNRS UMR 6521, CEMCA, SFR 148 ScInBios, 6 Avenue Victor Le Gorgeu, 29238 Brest (France)

    2016-04-15

    Novel physical or chemical properties are expected in a great variety of materials, in connection with the dimensionality of their structures and/or with their nanostructures, hierarchical superstructures etc. In the search of new advanced materials, the hydrothermal technique plays a crucial role, mimicking the nature able to produce fractal, hyperbranched, urchin-like or snow flake structures. In this short review including new results, this will be illustrated by examples selected in two types of materials, phosphates and phosphonates, prepared by this method. The importance of the synthesis parameters will be highlighted for a magnetic iron based phosphates and for hybrids containing phosphonates organic building units crystallizing in different structural types. - Graphical abstract: Phosphate dendrite like and phosphonate platelet crystals.

  10. High temperature proton exchange membranes prepared from epoxycyclohexylethyltrimethoxysilane and amino trimethylene phosphonic acid as anhydrous proton conductors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Cheng [Department of Polymer Materials and Engineering, School of Material Science and Engineering, Wuhan University of Technology, No. 122 Luoshi Road, Wuhan 430070 (China); Shen, Chunhui, E-mail: shenchunhui@whut.edu.cn [Department of Polymer Materials and Engineering, School of Material Science and Engineering, Wuhan University of Technology, No. 122 Luoshi Road, Wuhan 430070 (China); Kong, Gengjin; Gao, Shanjun [Department of Polymer Materials and Engineering, School of Material Science and Engineering, Wuhan University of Technology, No. 122 Luoshi Road, Wuhan 430070 (China)

    2013-06-15

    High temperature anhydrous proton exchange membranes based on phosphonic acid were prepared from epoxycyclohexylethyltrimethoxysilane (EHTMS) and amino trimethylene phosphonic acid (ATMP) by sol–gel process. The structures and properties of membranes with different phosphonic acid content were extensively characterized by FTIR, TG-DSC and XRD. Their proton conductivity under dry condition was also investigated under different temperature. The results show that the proton conductivity of the prepared membranes strongly depends on temperature, and the proton conductivity ranges from 8.81 × 10{sup −5} S cm{sup −1} at 20 °C to 4.65 × 10{sup −2} S cm{sup −1} at 140 °C under anhydrous condition. It indicates that the increasing temperature is favorable for congregating of the grafted–PO{sub 3}H{sub 2} and increasing of the proton mobility. In addition, from the results of AFM images, it was confirmed that the continuous distribution of phosphonic acid groups is favorable for the formation of the proton transport channel, which can significantly enhance the proton conductivity of the membranes. Highlights: ► Hybrid membranes of Epoxycyclohexylethyltrimethoxysilane and Amino trimethylene phosphonic acid. ► The proton conductivity is 4.65 × 10{sup −2} S cm{sup −1} at 140 °C under anhydrous condition. ► Continuous uniform distributions of phosphonic acid groups can be observed by AFM. ► There could be hydrogen bond network within high temperature membranes.

  11. Extraction of plutonium and uranium from oxalate bearing solutions using phosphonic acid

    International Nuclear Information System (INIS)

    Godbole, A.G.; Mapara, P.M.; Swarup, Rajendra

    1995-01-01

    A feasibility study on the solvent extraction of plutonium and uranium from solutions containing oxalic and nitric acids using a phosphonic acid extractant (PC88A) was made to explore the possibility of recovering Pu from these solutions. Batch experiments on the extraction of Pu(IV) and U(VI) under different parameters were carried out using PC88A in dodecane. The results indicated that Pu could be extracted quantitatively by PC88A from these solutions. A good separation of Pu from U could be achieved at higher temperatures. (author). 6 refs., 3 tabs

  12. Sustainable Catalytic Process for Synthesis of Triethyl Citrate Plasticizer over Phosphonated USY Zeolite

    Directory of Open Access Journals (Sweden)

    Kakasaheb Y. Nandiwaleand

    2016-10-01

    Full Text Available Fruits wastage is harmful to health and environment concerning spreading diseases and soil pollution, respectively. To avoid this issue, use of citrus fruit waste for the production of citric acid (CA is one of viable mean to obtain value added chemicals. Moreover, synthesis of triethyl citrate (TEC, a non-toxic plasticizer by esterification of CA with ethanol over heterogeneous catalyst would be renewable and sustainable catalytic process. In this context, parent Ultrastable Y (USY and different percentage phosphonated USY (P-USY zeolites were used for the synthesis of TEC in a closed batch reactor, for the first time. The synthesized catalysts were characterized by N2-adsorption desorption isotherm, powder X-ray diffraction (XRD and NH3 temperature programmed desorption (TPD. Effect of reaction conditions, such as the molar ratio of ethanol to CA (5:1 - 20:1, the catalyst to CA ratio (0.05 - 0.25 and reaction temperature (363-403 K, were studied in view to maximizing CA conversion and TEC yield. Phosphonated USY catalysts were found to be superior in activity (CA conversion and TEC yield than parent USY, which is attributed to the increased in total acidity with phosphonation. Among the studied catalysts, the P2USY (2% phosphorous loaded on USY was found to be an optimum catalyst with 99% CA conversion and 82% TEC yield, which is higher than the reported values. This study opens new avenues of research demonstrating principles of green chemistry such as easy separable and reusable catalyst, non-toxic product, bio-renewable synthetic route, milder operating parameters and waste minimization. Copyright © 2016 BCREC GROUP. All rights reserved Received: 12nd October 2015; Revised: 22nd December 2015; Accepted: 29th January 2016 How to Cite: Nandiwale, K.Y., Bokade, V.V. (2016. Sustainable Catalytic Process for Synthesis of Triethyl Citrate Plasticizer over Phosphonated USY Zeolite. Bulletin of Chemical Reaction Engineering & Catalysis, 11 (3: 292

  13. Tetramethyl guanidine (TMG catalyzed synthesis of novel a -amino phosphonates by one-pot reaction

    Directory of Open Access Journals (Sweden)

    S. Annar

    2010-07-01

    Full Text Available An efficient method has been developed for the synthesis of a -amino phosphonates (4a-j by the three component one-pot reaction of equimolar quantities of 2-amino methyl furan (1, dimethyl / diethyl phosphite (2 and various aldehydes (3a-j in dry toluene at reflux conditions via Kabachnik – Fields reaction in high yields (70-80% in the presence of tetramethyl guanidine (TMG as catalyst. The TMG can be easily recovered from the reaction mixture after completion of the reaction and can be reused. Their antimicrobial activity has also been evaluated.

  14. Supercritical Fluid Extraction (SFE) of uranium and thorium nitrates using carbon dioxide modified with phosphonates

    International Nuclear Information System (INIS)

    Pitchaiah, K.C.; Sujatha, K.; Brahmananda Rao, C.V.S.; Sivaraman, N.; Vasudeva Rao, P.R.

    2014-01-01

    Supercritical Fluid Extraction (SFE) has emerged as a powerful technique for the extraction of metal ions.The liquid like densities and gas like physical properties of supercritical fluids make them unique to act as special solvents. SFE based procedures were developed and demonstrated in our laboratory for the recovery of actinides from various matrices. In the present study, we have examined for the first time, the use of dialkylalkylphosphonates in supercritical carbon dioxide (Sc-CO 2 ) medium to study the extraction behavior of uranium and thorium nitrates. A series of phosphonates were synthesised by Michaelis-Becker reaction in our laboratory and employed for the SFE

  15. Metal phosphonate coordination networks and frameworks as precursors of electrocatalysts for the hydrogen and oxygen evolution reactions

    Science.gov (United States)

    Zhang, Rui; El-Refaei, Sayed M.; Russo, Patrícia A.; Pinna, Nicola

    2018-05-01

    The hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) play key roles in the conversion of energy derived from renewable energy sources into chemical energy. Efficient, robust, and inexpensive electrocatalysts are necessary for driving these reactions at high rates at low overpotentials and minimize energetic losses. Recently, electrocatalysts derived from hybrid metal phosphonate compounds have shown high activity for the HER or OER. We review here the utilization of metal phosphonate coordination networks and metal-organic frameworks as precursors/templates for transition-metal phosphides, phosphates, or oxyhydroxides generated in situ in alkaline solutions, and their electrocatalytic performance in HER or OER.

  16. Proton conducting graft copolymers with tunable length and density of phosphonated side chains for fuel cell membranes

    DEFF Research Database (Denmark)

    Dimitrov, Ivaylo; Takamuku, Shogo; Jankova Atanasova, Katja

    2014-01-01

    Polysulfones functionalized with highly phosphonated poly(pentafluorostyrene) side chains of different lengths were synthesized applying controlled polymerization and modification methods. The graft copolymers' thermal properties were evaluated by differential scanning calorimetry and thermal...... gravimetrical analyses. The proton conductivity of membrane prepared from the graft copolymer with the shortest phosphonated side chains was 134 mS cm(-1) at 100 degrees C under fully immersed conditions. The graft copolymer TEM image shows a nanophase separation of ion-rich segments within the polysulfone...

  17. Use of new phosphonylating and coupling agents in the synthesis of oligodeoxyribonucleotides via the H-phosphonate approach.

    OpenAIRE

    Sakatsume, O; Yamane, H; Takaku, H; Yamamoto, N

    1990-01-01

    New phosphonylating and coupling agents for the synthesis of oligodeoxyribonucleotides via H-phosphonate approach have been developed. Tris(1,1,1,3,3,3-hexafluoro-2-propyl) phosphite, prepared by the reaction of lithium salt of 1,1,1,3,3,3-hexafluoro-2-propoxide with PCl3, reacts with deoxyribonucleosides in the presence of a catalytic amount of triethylamine to produce in the high yield the corresponding deoxyribonucleoside 3'-H-phosphonate units. The use of a new coupling reagent, 1,3-dimet...

  18. Rhodium-Catalyzed Insertion Reaction of PhP Group of Pentaphenylcyclopentaphosphine with Acyclic and Cyclic Disulfides.

    Science.gov (United States)

    Arisawa, Mieko; Sawahata, Kyosuke; Yamada, Tomoki; Sarkar, Debayan; Yamaguchi, Masahiko

    2018-02-16

    Organophosphorus compounds with a phosphorus atom attached to a phenyl group and two organothio/organoseleno groups were synthesized using the rhodium-catalyzed insertion reaction of the PhP group of pentaphenylcyclopentaphosphine (PhP) 5 with acyclic disulfides and diselenides. The method was applied to the synthesis of heterocyclic compounds containing the S-P-S group by the reaction of (PhP) 5 and cyclic disulfides such as 1,2-dithietes, 1,2-dithiocane, 1,4,5-dithiopane, and 1,2-dithiolanes.

  19. 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.

  20. 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

  1. The effect of acyclic retinoid on the metabolomic profiles of hepatocytes and hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Xian-Yang Qin

    Full Text Available BACKGROUND/PURPOSE: Acyclic retinoid (ACR is a promising chemopreventive agent for hepatocellular carcinoma (HCC that selectively inhibits the growth of HCC cells (JHH7 but not normal hepatic cells (Hc. To better understand the molecular basis of the selective anti-cancer effect of ACR, we performed nuclear magnetic resonance (NMR-based and capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS-based metabolome analyses in JHH7 and Hc cells after treatment with ACR. METHODOLOGY/PRINCIPAL FINDINGS: NMR-based metabolomics revealed a distinct metabolomic profile of JHH7 cells at 18 h after ACR treatment but not at 4 h after ACR treatment. CE-TOFMS analysis identified 88 principal metabolites in JHH7 and Hc cells after 24 h of treatment with ethanol (EtOH or ACR. The abundance of 71 of these metabolites was significantly different between EtOH-treated control JHH7 and Hc cells, and 49 of these metabolites were significantly down-regulated in the ACR-treated JHH7 cells compared to the EtOH-treated JHH7 cells. Of particular interest, the increase in adenosine-5'-triphosphate (ATP, the main cellular energy source, that was observed in the EtOH-treated control JHH7 cells was almost completely suppressed in the ACR-treated JHH7 cells; treatment with ACR restored ATP to the basal levels observed in both EtOH-control and ACR-treated Hc cells (0.72-fold compared to the EtOH control-treated JHH7 cells. Moreover, real-time PCR analyses revealed that ACR significantly increased the expression of pyruvate dehydrogenase kinases 4 (PDK4, a key regulator of ATP production, in JHH7 cells but not in Hc cells (3.06-fold and 1.20-fold compared to the EtOH control, respectively. CONCLUSIONS/SIGNIFICANCE: The results of the present study suggest that ACR may suppress the enhanced energy metabolism of JHH7 cells but not Hc cells; this occurs at least in part via the cancer-selective enhancement of PDK4 expression. The cancer-selective metabolic pathways

  2. 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.

  3. Botanicals and Phosphonate Show Potential to Replace Copper for Control of Potato Late Blight

    Directory of Open Access Journals (Sweden)

    Hans-Rudolf Forrer

    2017-11-01

    Full Text Available Potato late blight (PLB caused by Phytophthora infestans (Pi is the most harmful disease in potato production worldwide. In organic farming, copper is used despite its persistence in soil and toxicity to soil organisms. To replace copper, suspensions of powders from three promising botanicals, including bark of buckthorn (Frangula alnus, FA, roots of medicinal rhubarb (Rheum palmatum and galls of the nutgall tree (Galla chinensis, were tested in multi-year field experiments. The current study shows for the first time that botanicals could replace copper under field conditions and best PLB reduction on leaves was achieved with FA, reaching a level close to that of 2 to 3 kg copper per hectare and year. Better results than with copper were achieved with Phosfik® (Ph, a phosphonate-based product. For both FA and Ph, the mode of action is based on induced resistance, for Ph also on direct fungicidal effects. A disadvantage of Ph is the accumulation of residues in potato tubers. Nevertheless, two to three applications with 2 to 3 L/ha of Ph would be feasible to not exceed a minimal risk level (MLR of 20 mg/kg of phosphorous acid as proposed by the European Food Safety Authority. Due to an excellent environmental profile and a complex mode of action counteracting Pi resistance, phosphonate-based products would be most suitable for sustainable PLB management in integrated pest management (IPM programmes.

  4. Phosphorus sorption on marine carbonate sediment: phosphonate as model organic compounds.

    Science.gov (United States)

    Huang, Xiao-Lan; Zhang, Jia-Zhong

    2011-11-01

    Organophosphonate, characterized by the presence of a stable, covalent, carbon to phosphorus (C-P) bond, is a group of synthetic or biogenic organophosphorus compounds. The fate of these organic phosphorus compounds in the environment is not well studied. This study presents the first investigation on the sorption of phosphorus (P) in the presence of two model phosphonate compounds, 2-aminothylphosphonoic acid (2-AEP) and phosphonoformic acid (PFA), on marine carbonate sediments. In contrast to other organic P compounds, no significant inorganic phosphate exchange was observed in seawater. P was found to adsorb on the sediment only in the presence of PFA, not 2-AEP. This indicated that sorption of P from phosphonate on marine sediment was compound specific. Compared with inorganic phosphate sorption on the same sediments, P sorption from organic phosphorus is much less in the marine environment. Further study is needed to understand the potential role of the organophosphonate compounds in biogeochemical cycle of phosphorus in the environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Covalent modification of calcium hydroxyapatite surface by grafting phenyl phosphonate moieties

    International Nuclear Information System (INIS)

    Aissa, Abdallah; Debbabi, Mongi; Gruselle, Michel; Thouvenot, Rene; Gredin, Patrick; Traksmaa, Rainer; Tonsuaadu, Kaia

    2007-01-01

    The reaction between phenyl phosphonic dichloride (C 6 H 5 P(O)Cl 2 ) and synthetic calcium hydroxy- and fluorapatite has been investigated. The presence of mono- or polymeric (C 6 H 5 PO) fragment bound to hydroxyapatite was evidenced by IR, and solid-state 31 P NMR spectroscopy. X-ray powder analysis has shown that the apatitic structure remains unchanged during the reaction. In contrast, no reaction was found using fluorapatite. According to the results found for these two different apatites a mechanism was proposed for the formation of covalent P-O-P bonds as the result of a reaction between the C 6 H 5 P(O)Cl 2 organic reagent and (HPO 4 ) - and/or OH - ions of the hydroxyapatite. - Graphical abstract: Representation of the first step of the reaction between the phenyl phosphonic dichloride and the hydroxyl groups on the surface of the apatite, leading to covalent P-O-P bond with elimination of HCl

  6. 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

  7. Comparative reactivity of different types of stable cyclic and acyclic mono- and diamino carbenes with simple organic substrates.

    Science.gov (United States)

    Martin, David; Canac, Yves; Lavallo, Vincent; Bertrand, Guy

    2014-04-02

    A series of stable carbenes, featuring a broad range of electronic properties, were reacted with simple organic substrates. The N,N-dimesityl imidazolylidene (NHC) does not react with isocyanides, whereas anti-Bredt di(amino)carbene (pyr-NHC), cyclic (alkyl)(amino)carbene (CAAC), acyclic di(amino)carbene (ADAC), and acyclic (alkyl)(amino)carbene (AAAC) give rise to the corresponding ketenimines. NHCs are known to promote the benzoin condensation, and we found that the CAAC, pyr-NHC, and ADAC react with benzaldehyde to give the ketone tautomer of the Breslow intermediate, whereas the AAAC first gives the corresponding epoxide and ultimately the Breslow intermediate, which can be isolated. Addition of excess benzaldehyde to the latter does not lead to benzoin but to a stable 1,3-dioxolane. Depending on the electronic properties of carbenes, different products are also obtained with methyl acrylate as a substrate. The critical role of the carbene electrophilicity on the outcome of reactions is discussed.

  8. Determination of acid-base dissociation constants of amino- and guanidinopurine nucleotide analogues and related compounds by capillary zone electroforesis

    Czech Academy of Sciences Publication Activity Database

    Šolínová, Veronika; Kašička, Václav; Koval, Dušan; Česnek, Michal; Holý, Antonín

    2006-01-01

    Roč. 27, č. 5/6 (2006), s. 1006-1019 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/03/0716; GA ČR(CZ) GA203/04/0098; GA AV ČR(CZ) 1QS400550501; GA MŠk(CZ) 1M0508; GA ČR(CZ) GA203/05/2539 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * capillary electrophoresis * dissociation constant Subject RIV: CC - Organic Chemistry Impact factor: 4.101, year: 2006

  9. Quantitative structure-property relationship (correlation analysis) of phosphonic acid-based chelates in design of MRI contrast agent.

    Science.gov (United States)

    Tiwari, Anjani K; Ojha, Himanshu; Kaul, Ankur; Dutta, Anupama; Srivastava, Pooja; Shukla, Gauri; Srivastava, Rakesh; Mishra, Anil K

    2009-07-01

    Nuclear magnetic resonance imaging is a very useful tool in modern medical diagnostics, especially when gadolinium (III)-based contrast agents are administered to the patient with the aim of increasing the image contrast between normal and diseased tissues. With the use of soft modelling techniques such as quantitative structure-activity relationship/quantitative structure-property relationship after a suitable description of their molecular structure, we have studied a series of phosphonic acid for designing new MRI contrast agent. Quantitative structure-property relationship studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors of the phosphonic acid-based chelating agent and their stability constants. The final quantitative structure-property relationship mathematical models were found as--quantitative structure-property relationship Model for phosphonic acid series (Model 1)--log K(ML) = {5.00243(+/-0.7102)}- MR {0.0263(+/-0.540)}n = 12 l r l = 0.942 s = 0.183 F = 99.165 quantitative structure-property relationship Model for phosphonic acid series (Model 2)--log K(ML) = {5.06280(+/-0.3418)}- MR {0.0252(+/- .198)}n = 12 l r l = 0.956 s = 0.186 F = 99.256.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. Complexation of 188Re-phosphonates: in vitro and in vivo studies

    International Nuclear Information System (INIS)

    Faintuch, B.L.; Muramoto, E.; Faintuch, S.

    2003-01-01

    MDP (methylenediphosphonate) and HEDP (hydroxyethylidene diphosphonate), both disphosphonates, and EDTMP (ethylenediamine tetramethylene phosphonic acid), a tetraphosphonate ligand, have been previously labeled with 188 Re for use in metastatic bone-pain palliation. The aim of this study was a comparison between the three complexes 188 Re-MDP, 188 Re-HEDP and 188 Re-EDTMP concerning the complexation conditions, in order to achieve maximum yield, stability and bone uptake. Methods: MDP was dissolved in water and HEDP and EDTMP were dissolved in NaOH 1 N followed by reduction of pH with HCl 1 N. To all mixtures stannous chloride and 188 ReO 4 - were added in a nitrogen atmosphere. The preparations were heated in boiling water bath for 15 min. Yield as well as radiochemical stability was estimated by ITLC. Different concentrations of phosphonates and stannous chloride were evaluated. Biodistribution studies in Swiss mice were done for the three 188 Re-phosphonates that presented the best radiochemical yield. The optimal ligand concentration for maximum complexation was 85.2 mM for MDP, 72.8 mM for HEDP and 45.8 mM for EDTMP. The best amount of SnCl 2 .2H 2 O was 1.5 mg/mL for 188 Re-HEDP and 1 mg/mL for both 188 Re-MDP and 188 Re-EDTMP. In these conditions the three complexes showed a complexation rate above 95%. Reasonable radiochemical stability for 24 hours was achieved by 188 Re-EDTMP when employing ascorbic acid. All products showed a great uptake by the kidneys. 188 Re-EDTMP had the greatest uptake by femur (3.1 ± 0.2% ID/g) followed by 188 Re-MDP (1.2 ± 0.1% ID/g) and 188 Re-HEDP (1.0 ± 0.1% ID/g), 4 hours post injection. 188 Re-EDTMP displayed a femur bone/muscle ratio of 28.5, 188 Re-MDP 4.9 and 188 Re-HEDP 4.9. In conclusion 188 Re-EDTMP demonstrated the best potential as a radiopharmaceutical for bone cancer pain relief, encouraging further dosimetric studies and clinical trials. (orig.)

  18. The development of Sm-153 EDTMP (ethylene diamine tetramethylene phosphonic acid), a bone seeking radiotherapeutic agent

    International Nuclear Information System (INIS)

    Rehir Dahalan; Wan Anuar Wan Awang; Shaaban Kassim

    1997-01-01

    Diagnostic radiopharmaceuticals have been the workhorse of nuclear medicine since it began in the early fifties, with the exception of radioiodine, which was also a therapeutic radiopharmaceutical. Over the years, significant advancement in the design of the diagnostic radiopharmaceuticals, have enabled optimum delivery of, the gamma emitting radionuclide to the target organs, whilst minimizing the dose to the non-target organs. This technology was utilized in this work, to deliver destructive beta emitting radionuclide to target cancerous tissues with the hope of slowing down or completely ablating its growth. This work had been in the production of Sm-153 using the MINT research reactor (MINTRR) and labeling it to the ethylene diamine tetramethylene phosphonic acid (EDTMP) ligand, a bone seeking complex. The results of this work have established the optimum labeling conditions and showed the biodistribution of the Sm-153 EDTMP complex in the rat

  19. 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

  20. Spectral, Electrochemical, Fluorescence, Kinetic and Anti-microbial Studies of Acyclic Schiff-base Gadolinium(III) Complexes

    International Nuclear Information System (INIS)

    Vijayaraj, A.; Prabu, R.; Suresh, R.; Narayanan, V.; Sangeetha Kumari, R.; Kaviyarasan, V.

    2012-01-01

    A new series of acyclic mononuclear gadolinium(III) complexes have been prepared by Schiff-base condensation derived from 5-methylsalicylaldehyde, diethylenetriamine, tris(2-aminoethyl) amine, triethylenetetramine, N,N-bis(3-aminopropyl)ethylene diamine, N,N-bis(aminopropyl) piperazine, and gadolinium nitrate. All the complexes were characterized by elemental and spectral analyses. Electronic spectra of the complexes show azomethine (CH=N) within the range of 410-420 nm. The fluorescence efficiency of Gd(III) ion in the cavity was completely quenched by the higher chain length ligands. Electrochemical studies of the complexes show irreversible one electron reduction process around -2.15 to -1.60 V. The reduction potential of gadolinium(III) complexes shifts towards anodic directions respectively upon increasing the chain length. The catalytic activity of the gadolinium(III) complexes on the hydrolysis of 4-nitrophenylphosphate was determined. All gadolinium(III) complexes were screened for antibacterial activity

  1. Spectral, Electrochemical, Fluorescence, Kinetic and Anti-microbial Studies of Acyclic Schiff-base Gadolinium(III) Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Vijayaraj, A.; Prabu, R.; Suresh, R.; Narayanan, V.; Sangeetha Kumari, R.; Kaviyarasan, V. [Univ. of Madras, Madras (India)

    2012-11-15

    A new series of acyclic mononuclear gadolinium(III) complexes have been prepared by Schiff-base condensation derived from 5-methylsalicylaldehyde, diethylenetriamine, tris(2-aminoethyl) amine, triethylenetetramine, N,N-bis(3-aminopropyl)ethylene diamine, N,N-bis(aminopropyl) piperazine, and gadolinium nitrate. All the complexes were characterized by elemental and spectral analyses. Electronic spectra of the complexes show azomethine (CH=N) within the range of 410-420 nm. The fluorescence efficiency of Gd(III) ion in the cavity was completely quenched by the higher chain length ligands. Electrochemical studies of the complexes show irreversible one electron reduction process around -2.15 to -1.60 V. The reduction potential of gadolinium(III) complexes shifts towards anodic directions respectively upon increasing the chain length. The catalytic activity of the gadolinium(III) complexes on the hydrolysis of 4-nitrophenylphosphate was determined. All gadolinium(III) complexes were screened for antibacterial activity.

  2. Acyclic Diene Metathesis (ADMET Polymerization for Precise Synthesis of Defect-Free Conjugated Polymers with Well-Defined Chain Ends

    Directory of Open Access Journals (Sweden)

    Tahmina Haque

    2015-03-01

    Full Text Available This accounts introduces unique characteristics by adopting the acyclic diene metathesis (ADMET polymerization for synthesis of conjugated polymers, poly(arylene vinylenes, known as promising molecular electronics. The method is more suitable than the other methods in terms of atom efficiency affording defect-free, stereo-regular (exclusive trans polymers with well-defined chain ends; the resultant polymers possess better property than those prepared by the conventional methods. The chain ends (vinyl group in the resultant polymer prepared by ruthenium-carbene catalyst(s can be modified by treating with molybdenum-alkylidene complex (olefin metathesis followed by addition of various aldehyde (Wittig type cleavage, affording the end-functionalized polymers exclusively. An introduction of initiating fragment, the other conjugated segment, and one-pot synthesis of end-functionalized block copolymers, star shape polymers can be achieved by adopting this methodology.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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+.

  8. Synthesis, crystal structures, and luminescent properties of two series' of new lanthanide (III) amino-carboxylate-phosphonates.

    Science.gov (United States)

    Zhou, Tian-Hua; Yi, Fei-Yan; Li, Pei-Xin; Mao, Jiang-Gao

    2010-02-01

    Hydrothermal reactions of lanthanide(III) chlorides with 4-HOOC-C(6)H(4)-CH(2)NHCH(2)PO(3)H(2) (H(3)L) at different ligand-to-metal (L/M) ratios afforded nine new lanthanide(III) carboxylate-phosphonates with two types of 3D network structures, namely, LnCl(HL)(H(2)O)(2) (Ln = Sm, 1; Eu, 2; Gd, 3; Tb, 4; Dy, 5; Er, 6) and [Ln(2)(HL)(H(2)L)(L)(H(2)O)(2)].4H(2)O (Ln = Nd, 7; Sm, 8; Eu, 9). Compounds 1-6 are isostructural and feature a 3D network in which the LnO(7)Cl polyhedra are interconnected by bridging CPO(3) tetrahedra into 2D inorganic layers parallel to the bc plane. These layers are further cross-linked by organic groups of the carboxylate-phosphonate ligands via the coordination of the carboxylate groups into a pillared-layered architecture. Compounds 7-9 are also isostructural and feature a 3D open-framework composed of 1D lanthanide(III) phosphonate inorganic slabs which are further bridged by organic groups of the carboxylate-phosphonate liagnds via the coordination of the carboxylate groups, forming large 1D tunnels along the b-axis which are filled by lattice water molecules. Luminescent measurements indicate that compounds 2, 4, and 5 show strong emission bands in red, green, and yellow light region, respectively. Magnetic properties of 2, 3, 5, and 7 have also been studied.

  9. Study of ion exchange behaviour of some elements at phosphonic-acid cationite in diluted solutions of nitric acid

    International Nuclear Information System (INIS)

    Razbash, A.A.; Sevast'yanov, Yu.G.

    1985-01-01

    Ce(3, 4), Eu(3), Gd(3), Sm(3), Sc(3) distribution coefficients are determined in the macroporic phosphonic acid cationite KRF-20T-60 in nitric acid solutions in 0.1-2.0 M concentration interval using statistical method. A simple method of cerium-139 radionuclide extraction from the industrial lanthanum target is developed. The product yield made up more than 99%, specific activity - 2.37x10 9 Bq/mg, radiochemical purity - no less than 99.9%

  10. Synthesis of highly phosphonic acid functionalized benzene-bridged periodic mesoporous organosilicas for use as efficient dye adsorbents

    International Nuclear Information System (INIS)

    Deka, Juti Rani; Liu, Chia-Ling; Wang, Tzu-Hua; Chang, Wei-Chieh; Kao, Hsien-Ming

    2014-01-01

    Highlights: • Synthesis of highly phosphonic acid functionalized benzene-bridged PMOs. • Phosphonic acid loaded PMOs as adsorbent for cationic and anionic dyes. • Due to electrostatic interaction the adsorbent has high dye adsorption capacity. • π–π stacking interaction between benzene and dye enhances adsorption capacity. • Intraparticle diffusion played a dominant role in the adsorption process. - Abstract: Periodic mesoporous organosilicas (PMOs) with benzene bridging groups in the silica wall were functionalized with a tunable content of phosphonic acid groups. These bifunctional materials were synthesized by co-condensation of two different organosilane precursors, that is, 1,4-bis(triethoxysilyl)benzene (BTEB) and sodium 3-(trihydroxysilyl)propyl methyl phosphate (SPMP), under acidic conditions using nonionic surfactant Brij-S10 as template. The materials exhibited well-ordered mesostructures and were characterized by X-ray diffraction, nitrogen sorption, TEM, TGA, FTIR, and solid-state NMR measurements. The materials thus obtained were employed as adsorbents to remove different types of dyes, for example, cationic dyes methylene blue and phenosafranine, anionic orange II, and amphoteric rhodamine B, from aqueous solutions. The materials exhibited a remarkably high adsorption capacity than activated carbon due to their ordered mesostructures, a large number of phosphonic acid groups, and high surface areas. The adsorption was mainly governed by electrostatic interaction, but also involved π–π stacking interaction as well as hydrogen bonding. The adsorption kinetics can be better fitted by the pseudo-second order model. The adsorption process was controlled by the mechanisms of external mass transfer and intraparticle diffusion. The materials retained more than 97% dye removal efficiency after use for five consecutive cycles

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. A functionalized phosphonate-rich organosilica layered hybrid material (PSLM) fabricated through a mild process for heavy metal uptake

    Energy Technology Data Exchange (ETDEWEB)

    Daikopoulos, Chris [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece); Bourlinos, Athanasios B. [Institute of Materials Science, NCSR “Demokritos”, Ag. Paraskevi Attikis, Athens 15310 (Greece); Georgiou, Yiannis [Laboratory of Physical Chemistry, Department of Environmental and Natural Resources Management, University of Patras, Seferi 2, Agrinio 30100 (Greece); Deligiannakis, Yiannis, E-mail: ideligia@cc.uoi.gr [Laboratory of Physical Chemistry, Department of Environmental and Natural Resources Management, University of Patras, Seferi 2, Agrinio 30100 (Greece); Zboril, Radek [Regional Centre of Advanced Technologies and Materials, Faculty of Science, Department of Physical Chemistry and Experimental Physics, Palacky University, Olomouc 77146 (Czech Republic); Karakassides, Michael A. [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece)

    2014-04-01

    Highlights: • Novel phosphonate-rich organosilica layered hybrid material (PSLM) fabricated through a mild xerogel process. • Surface Complexation Modeling reveals that PSLM bears 2 types of functional groups able to bind heavy metal. • Maximum metal uptake capacities were found 2.72 mmol g{sup −1} for Cu{sup 2+}, 1.67 mmol g{sup −1} for Pb{sup 2+} and 1.00 mmol g{sup −1} for Cd{sup 2+} at pH 7. • EPR spectroscopy reveals local coordination environment for Cu{sup 2+} ions. - Abstract: A phosphonate-rich organosilica layered hybrid material (PSLM) made of 3-(trihydroxysilyl)propyl methylphosphonate, monosodium salt, as the single silica source, has been obtained from its aqueous solution through a xerogel process and mild thermal aging. The method is simple, affording bulk quantities of powdered PSLM in a single-step. The hybrid is stable in water and possesses a high content of phosphonate groups fixed on the solid matrix. In addition, PSLM shows good thermal stability, which exceeds 300 °C in air. The material was characterized using SEM, TEM, XRD, FT-IR and TGA techniques. Potentiometric titrations show that PSLM bears high-surface density of phosphonate groups (3 mmol g{sup −1}). As a result, the material displays high metal uptake capacity for heavy metal ions such as Cu{sup 2+} (2.72 mmol g{sup −1}), Pb{sup 2+} (1.67 mmol g{sup −1}) and Cd{sup 2+} (1.00 mmol g{sup −1}) at neutral pH values e.g. the pH of natural waters. Detailed theoretical modeling using a Surface Complexation Model combined with Electron Paramagnetic Resonance (EPR) spectroscopy shows that the surface distribution of surface bound Cu{sup 2+} ions is rather homogeneous e.g. copper-binding phosphonate sites are arranged in average distances 5–8 Å.

  17. 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.

  18. 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....

  19. 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.)

  20. Syntheses and crystal structures of a series of new divalent metal phosphonates with imino-bis(methylphosphonic acid)

    International Nuclear Information System (INIS)

    Yang Bingping; Prosvirin, Andrey V.; Zhao, Han-Hua; Mao, Jiang-Gao

    2006-01-01

    Hydrothermal reactions of divalent transition metal salts with imino-bis(methylphosphonic acid), NH(CH 2 PO 3 H 2 ) 2 (H 4 L) afforded three new metal phosphonates, namely, Cu[NH(CH 2 PO 3 H) 2 ] 1, {Co[NH 2 (CH 2 PO 3 H)(CH 2 PO 3 )](H 2 O) 2 }.H 2 O 2 and Mn[NH 2 (CH 2 PO 3 H)(CH 2 PO 3 )](H 2 O) 3. When HO 2 C(CH 2 ) 3 N(CH 2 PO 3 H 2 ) 2 was used as the phosphonate ligand and 4,4'-bipy as the second metal linker, {Cu 4 [NH(CH 2 PO 3 ) 2 ] 2 (4,4'-bipy)(H 2 O) 4 }.9H 2 O 4 with a pillared layered architecture was obtained. The NH(CH 2 PO 3 ) 2 anion resulted from the cleavage of the HO 2 C(CH 2 ) 3 -group during the reaction. Although compounds 1-3 have a same M/L ratio (1:1), they exhibit totally different structures.Compound 1 has a linear chain structure, in which each pair of square-pyramidal coordinated copper(II) ions are bridged by two phosphonate oxygen atoms to form a Cu 2 O 2 dimeric unit, and such dimeric units are further interconnected via phosphonate groups to form a [010] chain. Compound 2 has a layered architecture built from CoO 6 octahedra bridged by phosphonate ligands. In compound 3, the interconnection of the manganese(II) ions by bridging imino-diphosphonate ligands leads to a 3D network. Compound 4 has a pillar-layered structure, the layers composed of Cu(II) ions bridged by aminodiphosphonate ligands are interconnected by 4,4'-bipy ligands to form channels along c-axis. Several factors that affect the structures of the metal phosphonates formed have also been discussed. Compounds 2 and 3 show predominant antiferromagnetic interactions between magnetic centers. -- Graphical abstract: Four new metal phosphonates, namely, Cu[NH(CH 2 PO 3 H) 2 ] 1, {Co[NH 2 (CH 2 PO 3 H)(CH 2 PO 3 )](H 2 O) 2 }.H 2 O 2, Mn[NH 2 (CH 2 PO 3 H)(CH 2 PO 3 )](H 2 O) 3 and {Cu 4 [NH(CH 2 PO 3 ) 2 ] 2 (4,4'-bipy)(H 2 O) 4 }.9H 2 O 4 have been synthesized and structurally characterized. Compound 1 has a linear chain structure, and compound 2 is layered. Compound 3 is

  1. Effects of radiation, acid, and base on the extractant dihexyl-[(diethylcarbamoyl)methyl] phosphonate

    International Nuclear Information System (INIS)

    Bahner, C.T.; Shoun, R.R.; McDowell, W.J.

    1981-11-01

    The effects of exposure to gamma radiation ( 60 Co) and of contact with acidic and basic aqueous solutions on dihexyl[(diethylcarbamoyl)methyl]phosphonate (DHDECMP) were studied. Gamma radiation decomposes DHDECMP into a variety of products. The most troublesome of those are the acidic compounds that cause problems in stripping the actinides and lanthanides from the extractant at low acid concentrations. The rate of degradation of DHDECMP by radiation is about the same or only slightly higher than that of tri-n-butyl phosphate (TBP). It is relatively easy to remove the radiation-produced impurities by equilibration (scrubbing) with sodium carbonate or sodium hydroxide or by column chromatographic methods. The hydrolysis of DHDECMP in contact with aqueous solutions containing less than 3 M HNO 3 is not more severe than that of TBP under the same conditions but is significant above that acid concentration. Hydrolysis of DHDECMP in contact with aqueous sodium hydroxide solution does occur, but it should not pose an important problem with the short contact times such as those anticipated for the removal of the radiation-induced degradation products by caustic scrubbing. Results of various chromatographic tests to characterize the degradation products of DHDECMP are also given

  2. Hydrothermal syntheses and anion-induced structural transformation of three Cadmium phosphonates

    Science.gov (United States)

    Hu, Han; Zhai, Fupeng; Liu, Xiaofeng; Ling, Yun; Chen, Zhenxia; Zhou, Yaming

    2018-05-01

    Three cadmium phosphonate coordinated polymers, namely as [Cd5(ptz)3(SO4)2(5H2O)]·6H2O (Cdptz-1), [Cd3(ptz)2(Cl)2(4H2O)]·2H2O (Cdptz-2) and [Cd4(ptz)2(SO4)(Cl)(OH)H2O]·H2O (Cdptz-3) have been hydrothermally synthesized using 4-(1,2,4-triazol-4-yl)phenylphosphonic acid (H2ptz) as ligand. Single crystal X-ray analyses revealed Cdptz-2 as layered structure and Cdptz-1,3 as pillar-layered structures with Cl- or SO42- as bridging anions. Due to the weak bonding between metal and anions, Cdptz-1 and 2 can reversibly convert into each other by simple immersing in the corresponding solution at room temperature. While the transformations between Cdptz-1,2 and Cdptz-3 can only happen under hydrothermal condition. The causes for the transformation involve the metal-ligand bond breaking/formation, replacement of anions and enhancement/decrement of the network dimensionality.

  3. Thermal and Dielectric Behavior Studies of Poly(Arylene Ether Sulfones with Sulfonated and Phosphonated Pendants

    Directory of Open Access Journals (Sweden)

    Shimoga D. Ganesh

    2016-01-01

    Full Text Available The present paper discusses the aspects of the synthesizing valeric acid based poly(ether sulfones with active carboxylic acid pendants (VALPSU from solution polymerization technique via nucleophilic displacement polycondensation reaction among 4,4′-dichlorodiphenyl sulfone (DCDPS and 4,4′-bis(4-hydroxyphenyl valeric acid (BHPA. The conditions necessary to synthesize and purify the polymer were investigated in some detail. The synthesized poly(ether sulfones comprise sulfone and ether linkages in addition to reactive carboxylic acid functionality; these active carboxylic acid functional groups were exploited to hold the phenyl sulphonic acid and phenyl phosphonic acid pendants. The phenyl sulphonic acid pendants in VALPSU were easily constructed by altering active carboxylic acid moieties by sulfanilic acid using N,N′-dicyclohexylcarbodiimide (DCC mediated mild synthetic route, whereas the latter one was built in two steps. Initially, polyphosphoric acid condensation with VALPSU by 4-bromoaniline and next straightforward palladium catalyzed synthetic route, in both of which acidic pendants are clenched by polymer backbone via amide linkage. Without impairing the primary polymeric backbone modified polymers were prepared by varying the stoichiometric ratios of respective combinations. All the polymers were physicochemically characterized and pressed into tablets; electrical contacts were established to study the dielectric properties. Finally, the influence of the acidic pendants on the dielectric properties was examined.

  4. Assembly of phosphonic acids on GaN and AlGaN

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, B S; Stine, R; Theodore, N D; Pehrsson, P E [Chemistry Division, Naval Research Laboratory, Washington DC (United States); Hong, S [Thomas Jefferson High School, McClean, VA (United States); Maekinen, A J [Optical Sciences Division, Naval Research Laboratory, Washington, DC (United States); Mastro, M A; Eddy, C R Jr [Electronics Science and Technology Division, Naval Research Laboratory, Washington, DC (United States)

    2010-01-13

    Self-assembled monolayers of octadecylphosphonic acid and 16-phosphonohexadecanoic acid (PHDA) were formed on the semiconductor substrates gallium nitride (GaN) and aluminium gallium nitride (AlGaN). The presence of the molecular layers was verified through x-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy. Structural information was acquired with infrared spectroscopy which verified the bonding orientation of the carboxyl-containing PHDA. The impact of the molecular layers on the channel conductivity and the surface electronic structure of an AlGaN/GaN heterostructure was measured. Our results indicate that pinning of the surface Fermi level prohibits modification of the channel conductivity by the layer. However, a surface dipole of {approx}0.8 eV is present and associated with both phosphonic acid layers. These results are of direct relevance to field-effect-based biochemical sensors and metal-semiconductor contact formation for this system and provide a fundamental basis for further applications of GaN and AlGaN technology in the fields of biosensing and microelectronics.

  5. 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.

  6. 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

  7. Adsorbed States of phosphonate derivatives of N-heterocyclic aromatic compounds, imidazole, thiazole, and pyridine on colloidal silver: comparison with a silver electrode.

    Science.gov (United States)

    Podstawka, Edyta; Olszewski, Tomasz K; Boduszek, Bogdan; Proniewicz, Leonard M

    2009-09-03

    Here, we report a systematic surface-enhanced Raman spectroscopy (SERS) study of the structures of phosphonate derivatives of the N-heterocyclic aromatic compounds imidazole (ImMeP ([hydroxy(1H-imidazol-5-yl)methyl]phosphonic acid) and (ImMe)(2)P (bis[hydroxy-(1H-imidazol-4-yl)-methyl]phosphinic acid)), thiazole (BAThMeP (butylaminothiazol-2-yl-methyl)phosphonic acid) and BzAThMeP (benzylaminothiazol-2-yl-methyl)phosphonic acid)), and pyridine ((PyMe)(2)P (bis[(hydroxypyridin-3-yl-methyl)]phosphinic acid)) adsorbed on nanometer-sized colloidal particles. We compared these structures to those on a roughened silver electrode surface to determine the relationship between the adsorption strength and the geometry. For example, we showed that all of these biomolecules interact with the colloidal surface through aromatic rings. However, for BzAThMeP, a preferential interaction between the benzene ring and the colloidal silver surface is observed more so than that between the thiazole ring and this substrate. The PC(OH)C fragment does not take part in the adsorption process, and the phosphonate moiety of ImMeP and (ImMe)(2)P, being removed from the surface, only assists in this process.

  8. Acyclic cucurbit[n]uril-type molecular containers: influence of glycoluril oligomer length on their function as solubilizing agents.

    Science.gov (United States)

    Gilberg, Laura; Zhang, Ben; Zavalij, Peter Y; Sindelar, Vladimir; Isaacs, Lyle

    2015-04-07

    We present the synthesis of a series of six new glycoluril derived molecular clips and acyclic CB[n]-type molecular containers (1–3) that all feature SO3(−) solubilizing groups but differ in the number of glycoluril rings between the two terminal dialkoxyaromatic sidewalls. We report the X-ray crystal structure of 3b which shows that its dialkoxynaphthalene sidewalls actively define a hydrophobic cavity with high potential to engage in π–π interactions with insoluble aromatic guests. Compounds 1–3 possess very good solubility characteristics (≥38 mM) and undergo only very weak self-association (Ks containers 3a and 3b which feature three glycoluril rings between the terminal dialkoxy-o-xylylene and dialkoxynaphthalene sidewalls are less efficient solubilizing agents than 4a and 4b because of their smaller hydrophobic cavities. Containers 1 and 2 behave as molecular clip type receptors and therefore possess the ability to bind to and thereby solubilize aromatic drugs like camptothecin, ziprasidone, and PBS-1086.

  9. Wavelet entropy and directed acyclic graph support vector machine for detection of patients with unilateral hearing loss in MRI scanning

    Directory of Open Access Journals (Sweden)

    Shuihua Wang

    2016-10-01

    Full Text Available (Aim Sensorineural hearing loss (SNHL is correlated to many neurodegenerative disease. Now more and more computer vision based methods are using to detect it in an automatic way. (Materials We have in total 49 subjects, scanned by 3.0T MRI (Siemens Medical Solutions, Erlangen, Germany. The subjects contain 14 patients with right-sided hearing loss (RHL, 15 patients with left-sided hearing loss (LHL, and 20 healthy controls (HC. (Method We treat this as a three-class classification problem: RHL, LHL, and HC. Wavelet entropy (WE was selected from the magnetic resonance images of each subjects, and then submitted to a directed acyclic graph support vector machine (DAG-SVM. (Results The 10 repetition results of 10-fold cross validation shows 3-level decomposition will yield an overall accuracy of 95.10% for this three-class classification problem, higher than feedforward neural network, decision tree, and naive Bayesian classifier. (Conclusions This computer-aided diagnosis system is promising. We hope this study can attract more computer vision method for detecting hearing loss.

  10. Reversible Twisting of Primary Amides via Ground State N-C(O) Destabilization: Highly Twisted Rotationally Inverted Acyclic Amides.

    Science.gov (United States)

    Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

    2018-01-17

    Since the seminal studies by Pauling in 1930s, planarity has become the defining characteristic of the amide bond. Planarity of amides has central implications for the reactivity and chemical properties of amides of relevance to a range of chemical disciplines. While the vast majority of amides are planar, nonplanarity has a profound effect on the properties of the amide bond, with the most common method to restrict the amide bond relying on the incorporation of the amide function into a rigid cyclic ring system. In a major departure from this concept, here, we report the first class of acyclic twisted amides that can be prepared, reversibly, from common primary amides in a single, operationally trivial step. Di-tert-butoxycarbonylation of the amide nitrogen atom yields twisted amides in which the amide bond exhibits nearly perpendicular twist. Full structural characterization of a range of electronically diverse compounds from this new class of twisted amides is reported. Through reactivity studies we demonstrate unusual properties of the amide bond, wherein selective cleavage of the amide bond can be achieved by a judicious choice of the reaction conditions. Through computational studies we evaluate structural and energetic details pertaining to the amide bond deformation. The ability to selectively twist common primary amides, in a reversible manner, has important implications for the design and application of the amide bond nonplanarity in structural chemistry, biochemistry and organic synthesis.

  11. Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2012-01-01

    Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

  12. Synthesis, spectroscopic and biological activities studies of acyclic and macrocyclic mono and binuclear metal complexes containing a hard-soft Schiff base.

    Science.gov (United States)

    Abou-Hussein, Azza A A; Linert, Wolfgang

    2012-09-01

    Mono- and bi-nuclear acyclic and macrocyclic complexes with hard-soft Schiff base, H(2)L, ligand derived from the reaction of 4,6-diacetylresorcinol and thiocabohydrazide, in the molar ratio 1:2 have been prepared. The H(2)L ligand reacts with Co(II), Ni(II), Cu(II), Zn(II), Mn(II) and UO(2)(VI) nitrates, VO(IV) sulfate and Ru(III) chloride to get acyclic binuclear complexes except for VO(IV) and Ru(III) which gave acyclic mono-nuclear complexes. Reaction of the acyclic mono-nuclear VO(IV) and Ru(III) complexes with 4,6-diacetylresorcinol afforded the corresponding macrocyclic mono-nuclear VO(IV) and Ru(IIII) complexes. Template reactions of the 4,6-diacetylresorcinol and thiocarbohydrazide with either VO(IV) or Ru(III) salts afforded the macrocyclic binuclear VO(IV) and Ru(III) complexes. The Schiff base, H(2)L, ligand acts as dibasic with two NSO-tridentate sites and can coordinate with two metal ions to form binuclear complexes after the deprotonation of the hydrogen atoms of the phenolic groups in all the complexes, except in the case of the acyclic mononuclear Ru(III) and VO(IV) complexes, where the Schiff base behaves as neutral tetradentate chelate with N(2)S(2) donor atoms. The ligands and the metal complexes were characterized by elemental analysis, IR, UV-vis (1)H-NMR, thermal gravimetric analysis (TGA) and ESR, as well as the measurements of conductivity and magnetic moments at room temperature. Electronic spectra and magnetic moments of the complexes indicate the geometries of the metal centers are either tetrahedral, square planar or octahedral. Kinetic and thermodynamic parameters were calculated using Coats-Redfern equation, for the different thermal decomposition steps of the complexes. The ligands and the metal complexes were screened for their antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria, and Pseudomonas fluorescens as Gram-negative bacteria in addition to Fusarium oxysporum fungus. Most of the complexes exhibit

  13. 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.

  14. 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

  15. 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...

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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)

  4. 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...

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. Effect of Time and Deposition Method on Quality of Phosphonic Acid Modifier Self-Assembled Monolayers on Indium Zinc Oxide

    Energy Technology Data Exchange (ETDEWEB)

    Sang, Lingzi; Knesting, Kristina M.; Bulusu, Anuradha; Sigdel, Ajaya K.; Giordano, Anthony J.; Marder, Seth R.; Berry, Joseph J.; Graham, Samuel; Ginger, David S.; Pemberton, Jeanne E.

    2016-12-15

    Phosphonic acid (PA) self-assembled monolayers (SAMs) are utilized at critical interfaces between transparent conductive oxides (TCO) and organic active layers in organic photovoltaic devices (OPVs). The effects of PA deposition method and time on the formation of close-packed, high-quality monolayers is investigated here for SAMs fabricated by solution deposition, micro-contact printing, and spray coating. The solution deposition isotherm for pentafluorinated benzylphosphonic acid (F5BnPA) on indium-doped zinc oxide (IZO) is studied using polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS) at room temperature as a model PA/IZO system. Fast surface adsorption occurs within the first min; however, well-oriented high-quality SAMs are reached only after -48 h, presumably through a continual process of molecular adsorption/desorption and monolayer filling accompanied by molecular reorientation. Two other rapid, soak-free deposition techniques, micro-contact printing and spray coating, are also explored. SAM quality is compared for deposition of phenyl phosphonic acid (PPA), F13-octylphosphonic acid (F13OPA), and pentafluorinated benzyl phosphonic acid (F5BnPA) by solution deposition, micro-contact printing and spray coating using PM-IRRAS. In contrast to micro-contact printing and spray coating techniques, 48-168 h solution deposition at both room temperature and 70 degrees C result in contamination- and surface etch-free close-packed monolayers with good reproducibility. SAMs fabricated by micro-contact printing and spray coating are much less well ordered.

  10. 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...

  11. Racemic cobalt phosphonates incorporating flexible bis(imidazole) co-ligands.

    Science.gov (United States)

    Feng, Jian-Shen; Cai, Zhong-Sheng; Ren, Min; Bao, Song-Song; Zheng, Li-Min

    2015-11-07

    By incorporating flexible bis(imidazol-1-ylmethyl)benzene (bix) co-ligands, four new racemic cobalt phosphonates with formulae Co3(3-ppap)2(1,4-bix)2(H2O)4·4H2O (1), Co3(3-ppap)2(1,3-bix)2(H2O)4·5H2O (2), Co3(3-ppap)2(1,2-bix)2(H2O)4·4H2O (3) and Co3(ppa)2(1,2-bix)2·4H2O (4) are isolated, where 3-ppapH3 represents 3-phenyl-3-((phosphonomethyl)amino)propanoic acid and ppaH3 is 2-phenyl-2-(phosphonomethylamino)acetic acid. Compounds 1-3 crystallize in the monoclinic space group P21/c and show two-dimensional structures in which the Co3(3-ppap)2 chains are bridged by 1,4-bix, 1,3-bix and 1,2-bix ligands in trans-modes, respectively. Within the chain, a racemic dimer of Co2(3-ppap)2(2-) is found, where the Co atoms are doubly bridged by O-P-O units from the (S)- and (R)-3-ppap(3-) ligands. The dimers are connected by another crystallographically independent Co atom through O-P-O linkages to form an infinite racemic chain. The packing modes of the layers in 1-3 are quite different, however, which are ABAB in the cases of 1 and 3 while ABCDABCD in the case of 2, attributed to the positional isomerism of the bix co-ligands. Compound 4 displays a chain structure in which the 1,2-bix bridges the Co atoms in cis-mode within the chain. Magnetic properties are investigated for all compounds.

  12. Properties of poly(lactic acid nanocomposites based on montmorillonite, sepiolite and zirconium phosphonate

    Directory of Open Access Journals (Sweden)

    K. Fukushima

    2012-11-01

    Full Text Available Poly(lactic acid (PLA based nanocomposites based on 5 wt.% of an organically modified montmorillonite (CLO, unmodified sepiolite (SEP and organically modified zirconium phosphonate (ZrP were obtained by melt blending. Wide angle X-ray scattering (WAXS and scanning electron microscopy (SEM analysis showed a different dispersion level depending on the type and functionalisation of nanoparticles. Differenctial scanning calorimetric (DSC analysis showed that PLA was able to crystallize on heating, and that the addition of ZrP could promote extent of PLA crystallization, whereas the presence of CLO and SEP did not significantly affect the crystallization on heating and melting behaviour of PLA matrix. Dynamic Mechanical Thermoanalysis (DMTA results showed that addition of all nanoparticles brought considerable improvements in E' of PLA, resulting in a remarkable increase of elastic properties for PLA nanocomposites. The melt viscosity and dynamic shear moduli (G',G" of PLA nanocomposites were also enhanced significantly by the presence of CLO and SEP, and attributed to the formation of a PLA/nanoparticle interconnected structure within the polymer matrix. The oxygen permeability of PLA did not significantly vary upon addition of SEP and ZrP nanoparticles. Only addition of CLO led to about 30% decrease compared to PLA permeability, due to the good clay dispersion and clay platelet-like morphology. The characteristic high transparency of PLA in the visible region was kept upon addition of the nanoparticles. Based on these achievements, a high potential of these PLA nanocomposites in sustainable packaging applications could be envisaged.

  13. Disorder-derived, strong tunneling attenuation in bis-phosphonate monolayers

    International Nuclear Information System (INIS)

    Pathak, Anshuma; Bora, Achyut; Tornow, Marc; Liao, Kung-Ching; Schwartz, Jeffrey; Schmolke, Hannah; Jung, Antje; Klages, Claus-Peter

    2016-01-01

    Monolayers of alkyl bisphosphonic acids (bisPAs) of various carbon chain lengths (C4, C8, C10, C12) were grown on aluminum oxide (AlO x ) surfaces from solution. The structural and electrical properties of these self-assembled monolayers (SAMs) were compared with those of alkyl monophosphonic acids (monoPAs). Through contact angle (CA) and Kelvin-probe (KP) measurements, ellipsometry, and infrared (IR) and x-ray photoelectron (XPS) spectroscopies, it was found that bisPAs form monolayers that are relatively disordered compared to their monoPA analogs. Current–voltage (J–V) measurements made with a hanging Hg drop top contact show tunneling to be the prevailing transport mechanism. However, while the monoPAs have an observed decay constant within the typical range for dense monolayers, β mono   =  0.85  ±  0.03 per carbon atom, a surprisingly high value, β bis   =  1.40  ±  0.05 per carbon atom, was measured for the bisPAs. We attribute this to a strong contribution of ‘through-space’ tunneling, which derives from conformational disorder in the monolayer due to strong interactions of the distal phosphonic acid groups; they likely form a hydrogen-bonding network that largely determines the molecular layer structure. Since bisPA SAMs attenuate tunnel currents more effectively than do the corresponding monoPA SAMs, they may find future application as gate dielectric modification in organic thin film devices. (paper)

  14. Disorder-derived, strong tunneling attenuation in bis-phosphonate monolayers

    Science.gov (United States)

    Pathak, Anshuma; Bora, Achyut; Liao, Kung-Ching; Schmolke, Hannah; Jung, Antje; Klages, Claus-Peter; Schwartz, Jeffrey; Tornow, Marc

    2016-03-01

    Monolayers of alkyl bisphosphonic acids (bisPAs) of various carbon chain lengths (C4, C8, C10, C12) were grown on aluminum oxide (AlO x ) surfaces from solution. The structural and electrical properties of these self-assembled monolayers (SAMs) were compared with those of alkyl monophosphonic acids (monoPAs). Through contact angle (CA) and Kelvin-probe (KP) measurements, ellipsometry, and infrared (IR) and x-ray photoelectron (XPS) spectroscopies, it was found that bisPAs form monolayers that are relatively disordered compared to their monoPA analogs. Current-voltage (J-V) measurements made with a hanging Hg drop top contact show tunneling to be the prevailing transport mechanism. However, while the monoPAs have an observed decay constant within the typical range for dense monolayers, β mono  =  0.85  ±  0.03 per carbon atom, a surprisingly high value, β bis  =  1.40  ±  0.05 per carbon atom, was measured for the bisPAs. We attribute this to a strong contribution of ‘through-space’ tunneling, which derives from conformational disorder in the monolayer due to strong interactions of the distal phosphonic acid groups; they likely form a hydrogen-bonding network that largely determines the molecular layer structure. Since bisPA SAMs attenuate tunnel currents more effectively than do the corresponding monoPA SAMs, they may find future application as gate dielectric modification in organic thin film devices.

  15. Sol–gel synthesis of tantalum oxide and phosphonic acid-modified carbon nanotubes composite coatings on titanium surfaces

    International Nuclear Information System (INIS)

    Maho, Anthony; Detriche, Simon; Delhalle, Joseph; Mekhalif, Zineb

    2013-01-01

    Carbon nanotubes used as fillers in composite materials are more and more appreciated for the outstanding range of accessible properties and functionalities they generate in numerous domains of nanotechnologies. In the framework of biological and medical sciences, and particularly for orthopedic applications and devices (prostheses, implants, surgical instruments, …), titanium substrates covered by tantalum oxide/carbon nanotube composite coatings have proved to constitute interesting and successful platforms for the conception of solid and biocompatible biomaterials inducing the osseous regeneration processes (hydroxyapatite growth, osteoblasts attachment). This paper describes an original strategy for the conception of resistant and homogeneous tantalum oxide/carbon nanotubes layers on titanium through the introduction of carbon nanotubes functionalized by phosphonic acid moieties (-P(=O)(OH) 2 ). Strong covalent C-P bonds are specifically inserted on their external sidewalls with a ratio of two phosphonic groups per anchoring point. Experimental results highlight the stronger “tantalum capture agent” effect of phosphonic-modified nanotubes during the sol–gel formation process of the deposits compared to nanotubes bearing oxidized functions (-OH, -C=O, -C(=O)OH). Particular attention is also paid to the relative impact of the rate of functionalization and the dispersion degree of the carbon nanotubes in the coatings, as well as their wrapping level by the tantalum oxide matrix material. The resulting effect on the in vitro growth of hydroxyapatite is also evaluated to confirm the primary osseous bioactivity of those materials. Chemical, structural and morphological features of the different composite deposits described herein are assessed by X-ray photoelectron spectroscopy (XPS), scanning (SEM) and transmission (TEM) electronic microscopies, energy dispersive X-rays analysis (EDX) and peeling tests. Highlights: ► Formation of tantalum/carbon nanotube

  16. Effect of time and deposition method on quality of phosphonic acid modifier self-assembled monolayers on indium zinc oxide

    Energy Technology Data Exchange (ETDEWEB)

    Sang, Lingzi [Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721 (United States); Knesting, Kristina M. [Department of Chemistry, University of Washington, Seattle, WA 98195-1700 (United States); Bulusu, Anuradha [School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Sigdel, Ajaya K. [National Renewable Energy Laboratory, Golden, CO 80401 (United States); Giordano, Anthony J.; Marder, Seth R. [School of Chemistry and Biochemistry and Center for Organic Photonics and Electronics, Georgia Institute of Technology, Atlanta, GA 30332-0400 (United States); Berry, Joseph J. [National Renewable Energy Laboratory, Golden, CO 80401 (United States); Graham, Samuel [School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Ginger, David S. [Department of Chemistry, University of Washington, Seattle, WA 98195-1700 (United States); Pemberton, Jeanne E., E-mail: pembertn@email.arizona.edu [Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721 (United States)

    2016-12-15

    Highlights: • Deposition of phosphonic acid monolayers on oxides from ethanol solutions occurs by rapid adsorption within 10 s with slower equilibration complete in 48 h. • The slower equilibration step involves molecular reorientation and vacancy filling on the oxide surface. • Soak-free deposition by spray coating and microcontact printing do not provide reproducible, fully-covered, uniform monolayers without substrate etching. • Adjustments to exposure time, substrate temperature, and solution/substrate contact efficiency are necessary to optimize soak-free methods. - Abstract: Phosphonic acid (PA) self-assembled monolayers (SAMs) are utilized at critical interfaces between transparent conductive oxides (TCO) and organic active layers in organic photovoltaic devices (OPVs). The effects of PA deposition method and time on the formation of close-packed, high-quality monolayers is investigated here for SAMs fabricated by solution deposition, micro-contact printing, and spray coating. The solution deposition isotherm for pentafluorinated benzylphosphonic acid (F{sub 5}BnPA) on indium-doped zinc oxide (IZO) is studied using polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS) at room temperature as a model PA/IZO system. Fast surface adsorption occurs within the first min; however, well-oriented high-quality SAMs are reached only after ∼48 h, presumably through a continual process of molecular adsorption/desorption and monolayer filling accompanied by molecular reorientation. Two other rapid, soak-free deposition techniques, micro-contact printing and spray coating, are also explored. SAM quality is compared for deposition of phenyl phosphonic acid (PPA), F{sub 13}-octylphosphonic acid (F{sub 13}OPA), and pentafluorinated benzyl phosphonic acid (F{sub 5}BnPA) by solution deposition, micro-contact printing and spray coating using PM-IRRAS. In contrast to micro-contact printing and spray coating techniques, 48–168 h solution

  17. Obtention of Samarium and Gadolinium concentrates by solvent extraction using mono-2-ethylhexyl ester of 2-ethylhexyl phosphonic acid

    International Nuclear Information System (INIS)

    Miranda Junior, Pedro

    1996-01-01

    The rare earth chlorides solution employed in this study, which is constituted by medium and heavy fractions, is derived from monazite processing accomplished by NUCLEMON-Mineroquimica (SP). This solution shows an acidity about 1.18 M and 189 g/L of rare earth oxides, containing as main constituents: Sm(34.55%), Gd(23.85%), Dy (6.82%), and Y (24.45%). It was used, as organic phase, 2-ethylhexyl phosphonic acid, mono-2-ethylhexylester diluted to 1 M in isododecane. (author)

  18. Sol–gel synthesis of tantalum oxide and phosphonic acid-modified carbon nanotubes composite coatings on titanium surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Maho, Anthony [Laboratory of Chemistry and Electrochemistry of Surfaces, University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Fonds pour la Formation à la Recherche dans l' Industrie et dans l' Agriculture (FRIA), Rue d' Egmont 5, B-1000 Bruxelles (Belgium); Detriche, Simon; Delhalle, Joseph [Laboratory of Chemistry and Electrochemistry of Surfaces, University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Mekhalif, Zineb, E-mail: zineb.mekhalif@fundp.ac.be [Laboratory of Chemistry and Electrochemistry of Surfaces, University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium)

    2013-07-01

    Carbon nanotubes used as fillers in composite materials are more and more appreciated for the outstanding range of accessible properties and functionalities they generate in numerous domains of nanotechnologies. In the framework of biological and medical sciences, and particularly for orthopedic applications and devices (prostheses, implants, surgical instruments, …), titanium substrates covered by tantalum oxide/carbon nanotube composite coatings have proved to constitute interesting and successful platforms for the conception of solid and biocompatible biomaterials inducing the osseous regeneration processes (hydroxyapatite growth, osteoblasts attachment). This paper describes an original strategy for the conception of resistant and homogeneous tantalum oxide/carbon nanotubes layers on titanium through the introduction of carbon nanotubes functionalized by phosphonic acid moieties (-P(=O)(OH){sub 2}). Strong covalent C-P bonds are specifically inserted on their external sidewalls with a ratio of two phosphonic groups per anchoring point. Experimental results highlight the stronger “tantalum capture agent” effect of phosphonic-modified nanotubes during the sol–gel formation process of the deposits compared to nanotubes bearing oxidized functions (-OH, -C=O, -C(=O)OH). Particular attention is also paid to the relative impact of the rate of functionalization and the dispersion degree of the carbon nanotubes in the coatings, as well as their wrapping level by the tantalum oxide matrix material. The resulting effect on the in vitro growth of hydroxyapatite is also evaluated to confirm the primary osseous bioactivity of those materials. Chemical, structural and morphological features of the different composite deposits described herein are assessed by X-ray photoelectron spectroscopy (XPS), scanning (SEM) and transmission (TEM) electronic microscopies, energy dispersive X-rays analysis (EDX) and peeling tests. Highlights: ► Formation of tantalum

  19. Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Honda, Masao; Yamashita, Taro; Yamashita, Tatsuya; Arai, Kuniaki; Sakai, Yoshio; Sakai, Akito; Nakamura, Mikiko; Mizukoshi, Eishiro; Kaneko, Shuichi

    2013-01-01

    The acyclic retinoid, peretinoin, has been shown to be effective for suppressing hepatocellular carcinoma (HCC) recurrence after definitive treatment in a small-scale randomized clinical trial. However, little has been documented about the mechanism by which peretinoin exerts its inhibitory effects against recurrent HCC in humans in vivo. Twelve hepatitis C virus-positive patients whose HCC had been eradicated through curative resection or ablation underwent liver biopsy at baseline and week 8 of treatment with either a daily dose of 300 or 600 mg peretinoin. RNA isolated from biopsy samples was subjected to gene expression profile analysis. Peretinoin treatment elevated the expression levels of IGFBP6, RBP1, PRB4, CEBPA, G0S2, TGM2, GPRC5A, CYP26B1, and many other retinoid target genes. Elevated expression was also observed for interferon-, Wnt-, and tumor suppressor-related genes. By contrast, decreased expression levels were found for mTOR- and tumor progression-related genes. Interestingly, gene expression profiles for week 8 of peretinoin treatment could be classified into two groups of recurrence and non-recurrence with a prediction accuracy rate of 79.6% (P<0.05). In the liver of patients with non-recurrence, expression of PDGFC and other angiogenesis genes, cancer stem cell marker genes, and genes related to tumor progression was down-regulated, while expression of genes related to hepatocyte differentiation, tumor suppression genes, and other genes related to apoptosis induction was up-regulated. Gene expression profiling at week 8 of peretinoin treatment could successfully predict HCC recurrence within 2 years. This study is the first to show the effect of peretinoin in suppressing HCC recurrence in vivo based on gene expression profiles and provides a molecular basis for understanding the efficacy of peretinoin

  20. 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

  1. Understanding the interactions of phosphonate-based flame-retarding additives with graphitic anode for lithium ion batteries

    International Nuclear Information System (INIS)

    Feng, Jinkui; Ma, Peng; Yang, Hanxi; Lu, Li

    2013-01-01

    Highlights: •Diethyl ethylphosphonate (DEEP) and dimethyl methylphosphonate are tested as flame retardants for lithium ion batteries. •The DMMP shows a destructive reaction with graphitic anode while DEEP shows a self-reduction mechanism. •DEEP is reported for the first time as flame-retardant additive for lithium ion batteries and demonstrates a much better compatibility with graphitic anode. -- Abstract: The compatibility with graphitic anode has been one key problem in developing flame-retarding additives for lithium ion batteries. To understand the interactions between flame-retarding additives and graphitic anode, two phosphonate esters (dimethyl methylphosphonate DMMP and diethyl ethylphosphonate DEEP) are selected and characterized as flame retardant addtives. DEEP is reported as a flame-retarding additive for the first time. Their interactions with graphite anode are characterized via current-static charge–discharge, ex-situ XRD, FE-SEM and AC impedance. The results reveal that the two phosphonate esters demonstrate different reaction mechanisms with graphitic anode, which result in different anode compatibility. These findings may be useful for designing better flame-retarding additives for lithium ion batteries

  2. SBA-15 mesoporous silica free-standing thin films containing copper ions bounded via propyl phosphonate units - preparation and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Laskowski, Lukasz, E-mail: lukasz.laskowski@kik.pcz.pl [Czestochowa University of Technology, Institute of Computational Intelligence, Unit of Microelectronics and Nanotechnology, Al. Armii Krajowej 36, 42–201 Czestochowa (Poland); Laskowska, Magdalena, E-mail: magdalena.laskowska@onet.pl [H. Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, ul. Radzikowskiego 152 (Poland); Jelonkiewicz, Jerzy, E-mail: jerzy.jelonkiewicz@kik.pcz.pl [Czestochowa University of Technology, Institute of Computational Intelligence, Unit of Microelectronics and Nanotechnology, Al. Armii Krajowej 36, 42–201 Czestochowa (Poland); Dulski, Mateusz, E-mail: mateusz.dulski@us.edu.pl [University of Silesia, Faculty of Computer Science and Materials Science, Institute of Materials Science, Silesian Center for Education and Interdisciplinary Research, ul. 75 Pułku Piechoty 1A, 41–500 Chorzów (Poland); Wojtyniak, Marcin, E-mail: marcin.wojtyniak@us.edu.pl [University of Silesia, Institute of Physics, Silesian Center for Education and Interdisciplinary Research, ul. 75 Pułku Piechoty 1A, 41–500 Chorzów (Poland); Fitta, Magdalena, E-mail: magdalena.fitta@ifj.edu.pl [H. Niewodniczański Institute of Nuclear Physics, Polish Academy of Sciences, 31–342 Krakow, ul. Radzikowskiego 152 (Poland); Balanda, Maria, E-mail: Maria.Balanda@ifj.edu.pl [H. Niewodniczański Institute of Nuclear Physics, Polish Academy of Sciences, 31–342 Krakow, ul. Radzikowskiego 152 (Poland)

    2016-09-15

    The SBA-15 silica thin films containing copper ions anchored inside channels via propyl phosphonate groups are investigated. Such materials were prepared in the form of thin films, with hexagonally arranged pores, laying rectilinear to the substrate surface. However, in the case of our thin films, their free standing form allowed for additional research possibilities, that are not obtainable for typical thin films on a substrate. The structural properties of the samples were investigated by X-ray reflectometry, atomic force microscopy (AFM) and transmission electron microscopy (TEM). The molecular structure was examined by Raman spectroscopy supported by numerical simulations. Magnetic measurements (SQUID magnetometry and EPR spectroscopy) showed weak antiferromagnetic interactions between active units inside silica channels. Consequently, the pores arrangement was determined and the process of copper ions anchoring by propyl phosphonate groups was verified in unambiguous way. Moreover, the type of interactions between magnetic atoms was determined. - Highlights: • Functionalized free-standing SBA-15 thin films were synthesized for a first time. • Thin films synthesis procedure was described in details. • Structural properties of the films were thoroughly investigated and presented. • Magnetic properties of the novel material was investigated and presented.

  3. Prevention of refinery plugging by residual oil gellant chemicals in crude-optimization of phosphonate ester oil gellants

    Energy Technology Data Exchange (ETDEWEB)

    Lemieux, A.; Alick, C.; Stadnyk, S.; Funkhouser, G.; Fyten, G.; Taylor, R.S. [Halliburton Energy Services, Calgary, AB (Canada); Stemler, P. [Petro-Canada Oil and Gas Inc., Calgary, AB (Canada)

    2005-07-01

    This study examined the use of phosphonate ester oil gellants for refinery plugging. Field tests were performed to test ways to optimize cost and performance and to establish quality control specifications based on performance testing and compositional analysis determined through nuclear magnetic resonance (NMR). Additional field tests were performed to ensure both operational performance and the ability to control volatile phosphorus while continuing to meet the standards of the 2 initial field trials. The study assessed the ability of phosphonate esters to control volatile phosphorus at higher temperatures. Distillations used to evaluate volatile phosphorus to date have had a 250 degree C end point. This temperature was chosen because it represents the approximate temperature experienced at the distillation tower trays where plugging has been observed from components condensing from the gas phase. However, the actual peak temperature in the tower bottom is closer to 350 degrees C. This higher temperature is the actual temperature at which decomposition or volatilization occurs. In order to fully understand the ability to control volatile phosphorus, distillations were conducted with a 350 degree C end point. Volatile and total phosphorus to both 250 degrees C and 350 degrees C end points were reported. The study also addressed the concern regarding organic halide formation under distillation tower conditions, although no organic halides were detected in the field trials. 3 refs., 2 tabs., 7 figs.

  4. Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ross, Ryan D. [Rush University Medical Center, Department of Anatomy and Cell Biology (United States); Cole, Lisa E.; Roeder, Ryan K., E-mail: rroeder@nd.edu [University of Notre Dame, Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program (United States)

    2012-10-15

    Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate (l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

  5. A novel glucose biosensor based on phosphonic acid-functionalized silica nanoparticles for sensitive detection of glucose in real samples

    International Nuclear Information System (INIS)

    Zhao, Wenbo; Fang, Yi; Zhu, Qinshu; Wang, Kuai; Liu, Min; Huang, Xiaohua; Shen, Jian

    2013-01-01

    An effective strategy for preparation amperometric biosensor by using the phosphonic acid-functionalized silica nanoparticles (PFSi NPs) as special modified materials is proposed. In such a strategy, glucose oxidase (GOD) was selected as model protein to fabricate glucose biosensor in the presence of phosphonic acid-functionalized silica nanoparticles (PFSi NPs). The PFSi NPs were first modified on the surface of glassy carbon (GC) electrode, then, GOD was adsorbed onto the PFSi NPs film by drop-coating. The PFSi NPs were characterized by transmission electron microscopy (TEM) and nuclear magnetic resonance (NMR) spectra. The interaction of PFSi NPs with GOD was investigated by the circular dicroism spectroscopy (CD). The results showed PFSi NPs could essentially maintain the native conformation of GOD. The direct electron transfer of GOD on (PFSi NPs)/GCE electrode exhibited excellent electrocatalytic activity for the oxidation of glucose. The proposed biosensor modified with PFSi NPs displayed a fast amperometric response (5 s) to glucose, a good linear current–time relation over a wide range of glucose concentrations from 5.00 × 10 −4 to 1.87 × 10 −1 M, and a low detection limit of 2.44 × 10 −5 M (S/N = 3). Moreover, the biosensor can be used for assessment of the concentration of glucose in many real samples (relative error < 3%). The GOD biosensor modified with PFSi NPs will have essential meaning and practical application in future that attributed to the simple method of fabrication and good performance

  6. Experimental and in silico investigations of organic phosphates and phosphonates sorption on polymer-ceramic monolithic materials and hydroxyapatite.

    Science.gov (United States)

    Pietrzyńska, Monika; Zembrzuska, Joanna; Tomczak, Rafał; Mikołajczyk, Jakub; Rusińska-Roszak, Danuta; Voelkel, Adam; Buchwald, Tomasz; Jampílek, Josef; Lukáč, Miloš; Devínsky, Ferdinand

    2016-10-10

    A method based on experimental and in silico evaluations for investigating interactions of organic phosphates and phosphonates with hydroxyapatite was developed. This quick and easy method is used for determination of differences among organophosphorus compounds of various structures in their mineral binding affinities. Empirical sorption evaluation was carried out using liquid chromatography with tandem mass spectrometry or UV-VIS spectroscopy. Raman spectroscopy was used to confirm sorption of organic phosphates and phosphonates on hydroxyapatite. Polymer-ceramic monolithic material and bulk hydroxyapatite were applied as sorbent materials. Furthermore, a Polymer-ceramic Monolithic In-Needle Extraction device was used to investigate both sorption and desorption steps. Binding energies were computed from the fully optimised structures utilising Density Functional Theory (DFT) at B3LYP/6-31+G(d,p) level. Potential pharmacologic and toxic effects of the tested compounds were estimated by the Prediction of the Activity Spectra of Substances using GeneXplain software. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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...

  8. 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.

  9. Novel alpha-zirconium phosphonates for the reinforcement of ductile thermoplastics

    Science.gov (United States)

    Furman, Benjamin R.

    2007-12-01

    Ductile thermoplastics are useful additives for providing fracture toughness to brittle thermosetting polymers; however, this toughening is usually accompanied by a significant decrease in elastic modulus. Therefore, alpha-zirconium phosphonates (ZrP) were developed and investigated as reinforcing nano-scale fillers that increase the yield strength and elastic modulus of a polyester thermoplastic without causing a reduction in its ductility. ZrP materials are synthetic layered compounds that are imbued with targeted organic surface functionalities and whose structural development can be carefully controlled in the laboratory. Ether-terminal alkyl ZrP materials were designed and synthesized, using a conventional ZrF62--mediated preparation, with the intent of developing strong dipole-dipole interactions between the layer surfaces and polyester macromolecules. Additionally, a general method for using lamellar lyotropic liquid crystals (LLC's) as supramolecular templates for alkyl ZrP was evaluated, whose products showed promising similarity to the conventionally prepared materials. The LLC-forming characteristics of several organophosphonate preparations were determined, showing improved mesophase stability with mixed amphiphiles and preparation with R4N + counterions. A mixed-surface octyl/methoxyundecyl ZrP was produced and combined with polycaprolactone (PCL) and polymethylmethacrylate (PMMA) in concentrations up to 50% (w/w). The mechanical properties of the ZrP/PCL nanocomposite were evaluated by tensile, flexural, and dynamic mechanical testing methods. Nanocomposites containing 5% (w/w) ZrP showed significant increases in tensile yield stress and elastic modulus without suffering any loss of ductility versus the unfilled polymer. Layer delamination from the ZrP tactoids was minimal and did not occur through an intercalative mechanism. Higher ZrP loadings resulted in the agglomeration of tactoids, leading to defect structures and loss of strength and ductility

  10. Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

    International Nuclear Information System (INIS)

    Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

    2015-01-01

    177 Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177 Lu-EDTMP for MBP palliation. 177 Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177 Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177 Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

  11. Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid.

    Science.gov (United States)

    Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R; Bahrami-Samani, Ali

    2015-01-01

    (177)Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using (177)Lu-EDTMP for MBP palliation. (177)Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. (177)Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. (177)Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

  12. Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

    Science.gov (United States)

    Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

    2015-01-01

    177Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177Lu-EDTMP for MBP palliation. 177Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients

  13. 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.

  14. 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).

  15. Flame-retardant copolymers of dialkyl (meth)acryloyloxyalkyl phosphate or dialkyl (meth)acryloyloxyalkyl phosphonate monomers and polymer foams based made therefrom

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Yudong; Li, Yan; Bunker, Shana P.; Costeux, Stephane; Morgan, Ted A.

    2017-12-12

    Polymer foam bodies are made from phosphorus-containing thermoplastic random copolymers of a dialkyl (meth)acryloyloxyalkyl phosph(on)ate. Foam bodies made from these copolymers exhibit increased limiting oxygen indices and surprisingly have good properties. In certain embodiments, the phosphorus-containing thermoplastic copolymer is blended with one or more other polymers and formed into nanofoams.

  16. Novel sulfonated poly (ether ether ketone)/phosphonic acid-functionalized titania nanohybrid membrane by an in situ method for direct methanol fuel cells

    Science.gov (United States)

    Wu, Hong; Cao, Ying; Li, Zhen; He, Guangwei; Jiang, Zhongyi

    2015-01-01

    Sulfonated poly (ether ether ketone)/phosphonic acid-functionalized titania nanohybrid membranes are prepared by an in situ method using titanium tetrachloride (TiCl4) as inorganic precursor and amino trimethylene phosphonic acid (ATMP) as modifier. Phosphonic acid-functionalized titania nanoparticles with a uniform particle size of ∼50 nm are formed and dispersed homogeneously in the SPEEK matrix with good interfacial compatibility. Accordingly, the nanohybrid membranes display remarkably enhanced proton conduction property due to the incorporation of additional sites for proton transport and the formation of well-connected channels by bridging the hydrophilic domains in SPEEK matrix. The nanohybrid membrane with 6 wt. % of phosphonic acid-functionalized titania nanoparticles exhibits the highest proton conductivity of 0.334 S cm-1 at 65 °C and 100% RH, which is 63.7% higher than that of pristine SPEEK membrane. Furthermore, the as-prepared nanohybrid membranes also show elevated thermal and mechanical stabilities as well as decreased methanol permeability.

  17. 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

  18. 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

  19. 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...

  20. 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

  1. Flexible Acyclic Polyol-Chloride Anion Complexes and Their Characterization by Photoelectron Spectroscopy and Variable Temperature Binding Constant Determinations

    Energy Technology Data Exchange (ETDEWEB)

    Shokri, Alireza; Wang, Xue B.; Wang, Yangping; O' Doherty, George A.; Kass, Steven R.

    2016-03-17

    Flexible acyclic alcohols with 1–5 hydroxyl groups were bound to chloride anion and these complexes were interrogated by negative ion photoelectron spectroscopy and companion density functional theory computations. The resulting vertical detachment energies are reproduced on average to 0.10 eV by M06-2X/aug-cc-pVTZ predictions and range from 4.45 – 5.96 eV. These values are 0.84 – 2.35 eV larger than the adiabatic detachment energy of Cl– as a result of the larger hydrogen bond networks in the bigger polyols. Adiabatic detachment energies of the alcohol–Cl– clusters are more difficult to determine both experimentally and computationally. This is due to the large geometry changes that occur upon photodetachment and the large bond dissociation energy of H–Cl which enables the resulting chlorine atom to abstract a hydrogen from any of the methylene (CH2) or methine (CH) positions. Both ionic and non-ionic hydrogen bonds (i.e., OH•••Cl– and OH•••OH•••Cl–) form in the larger polyols complexes, and are found to be energetically comparable. Subtle structural differences, consequently can lead to the formation of different types of hydrogen bonds and maximizing the ionic ones is not always preferred. Solution equilibrium binding constants between the alcohols and tetrrabuylammonium chloride (TBACl) in acetonitrile at -24.2, 22.0, and 53.6 °C were also determined. The free energies of association are nearly identical for all of the substrates (i.e., ΔG° = -2.8 ± 0.7 kcal mol–1). Compensating enthalpy and entropy values reveal, contrary to expectation and the intrinsic gas-phase preferences, that the bigger systems with more hydroxyl groups are entropically favored and enthalpically disfavored relative to the smaller species. This suggests that more solvent molecules are released upon binding TBACl to alcohols with more hydroxyl groups and is consistent with the measured negative heat capacities. These quantities increase with

  2. 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

  3. 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.

  4. [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.

  5. Acyclic cucurbit[n]uril-type molecular containers: influence of aromatic walls on their function as solubilizing excipients for insoluble drugs.

    Science.gov (United States)

    Zhang, Ben; Isaacs, Lyle

    2014-11-26

    We studied the influence of the aromatic sidewalls on the ability of acyclic CB[n]-type molecular containers (1a-1e) to act as solubilizing agents for 19 insoluble drugs including the developmental anticancer agent PBS-1086. All five containers exhibit good water solubility and weak self-association (Ks ≤ 624 M(-1)). We constructed phase solubility diagrams to extract Krel and Ka values for the container·drug complexes. The acyclic CB[n]-type containers generally display significantly higher Ka values than HP-β-CD toward drugs. Containers 1a-1e bind the steroidal ring system and aromatic moieties of insoluble drugs. Compound 1b displays highest affinity toward most of the drugs studied. Containers 1a and 1b are broadly applicable and can be used to formulate a wider variety of insoluble drugs than was previously possible with cyclodextrin technology. For drugs that are solubilized by both HP-β-CD and 1a-1e, lower concentrations of 1a-1e are required to achieve identical [drug].

  6. Conformational analysis of an acyclic tetrapeptide: ab-initio structure determination from X-ray powder diffraction, Hirshfeld surface analysis and electronic structure.

    Science.gov (United States)

    Das, Uday; Naskar, Jishu; Mukherjee, Alok Kumar

    2015-12-01

    A terminally protected acyclic tetrapeptide has been synthesized, and the crystal structure of its hydrated form, Boc-Tyr-Aib-Tyr-Ile-OMe·2H2O (1), has been determined directly from powder X-ray diffraction data. The backbone conformation of tetrapeptide (1) exhibiting two consecutive β-turns is stabilized by two 4 → 1 intramolecular N-H · · · O hydrogen bonds. In the crystalline state, the tetrapeptide molecules are assembled through water-mediated O-H · · · O hydrogen bonds to form two-dimensional molecular sheets, which are further linked by intermolecular C-H · · · O hydrogen bonds into a three-dimensional supramolecular framework. The molecular electrostatic potential (MEP) surface of (1) has been used to supplement the crystallographic observations. The nature of intermolecular interactions in (1) has been analyzed quantitatively through the Hirshfeld surface and two-dimensional fingerprint plot. The DFT optimized molecular geometry of (1) agrees closely with that obtained from the X-ray structure analysis. The present structure analysis of Boc-Tyr-Aib-Tyr-Ile-OMe·2H2 O (1) represents a case where ab-initio crystal structure of an acyclic tetrapeptide with considerable molecular flexibility has been accomplished from laboratory X-ray powder diffraction data. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  7. Preparation, characterization and application of N-methylene phosphonic acid chitosan grafted magnesia–zirconia stationary phase

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qing; Chen, Jie; Huang, Kun; Zhang, Xin; Xu, Li [Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030 (China); Shi, Zhi-guo, E-mail: shizg@whu.edu.cn [Department of Chemistry, Wuhan University, Wuhan 430072 (China)

    2015-01-07

    Highlights: • N-methylene phosphonic acid chitosan grafted MgO–ZrO{sub 2} was prepared. • It exhibited superior HILIC chromatographic performance to the bare MgO–ZrO{sub 2}. • Monosaccharides, phospholipids and peptides were successfully separated. • It was a promising HILIC stationary phase. - Abstract: A hydrophilic stationary phase (SP) was prepared through grafting N-methylene phosphonic acid chitosan on magnesia–zirconia particles (P-CTS-MgO–ZrO{sub 2}) via Lewis acid–base interaction. The resulting material was characterized by thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscope and nitrogen adsorption analysis. The chromatographic performance of P-CTS-MgO–ZrO{sub 2} was systemically evaluated by studying effect of acetonitrile content, pH and buffer concentration in the mobile phase. The results demonstrated that the novel SP provided hydrophilic, electrostatic-repulsion and ion-exchange interactions. Compared to the bare MgO–ZrO{sub 2}, P-CTS-MgO–ZrO{sub 2} exhibited superior peak shape, reasonable resolution and reduced analysis time in separation of basic analytes. Besides, remarkable resolving power of acids, i.e. six non-steroidal anti-inflammatory drugs which failed to be eluted from the bare MgO–ZrO{sub 2}, was obtained with the theoretical plate number (N/m) of 4653–31313, asymmetry factor <1.21 and the resolution of 1.6–3.4. Finally, P-CTS-MgO–ZrO{sub 2} SP was applied to separate monosaccharides, phospholipids and peptides. P-CTS-MgO–ZrO{sub 2} was a promising hydrophilic SP for wide applications.

  8. Antitenascin antibody 81C6 armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Yordanov, Alexander T. [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States); Hens, Marc [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States); Pegram, Charles [Department of Pathology, Duke University Medical Center Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States)]. E-mail: zalut001@mc.duke.edu

    2007-02-15

    Introduction: When labeled with iodine-131, the antitenascin monoclonal antibody (mAb) 81C6 has shown promise as a targeted radiotherapeutic in patients with brain tumors. Because of its more favorable {gamma}-ray properties, lutetium-177 might be a better low-energy {beta}-emitter for this type of therapy. Materials and Methods: Chimeric 81C6 (ch81C6) was labeled with {sup 177}Lu using the acyclic 1B4M ligand and the macrocyclic ligands NHS-DOTA and MeO-DOTA and evaluated for binding to tenascin. Three paired-label tissue distribution experiments were performed in normal mice receiving one of the {sup 177}Lu-labeled immunoconjugates plus {sup 125}I-labeled ch81C6 labeled using Iodogen. Paired-label experiments in athymic mice bearing subcutaneous D54 MG human glioma xenografts were done to directly compare the biodistribution of ch81C6-1B4M-{sup 177}Lu and {sup 125}I-labeled ch81C6, and ch81C6-MeO-DOTA-{sup 177}Lu and {sup 125}I-labeled ch81C6. Similar comparisons were done using murine (mu) instead of ch81C6. The primary parameter utilized for evaluation was the {sup 177}Lu/{sup 125}I uptake ratio in each tissue. Results: In the studies performed in normal mice, the NHS-DOTA ligand yielded the highest {sup 177}Lu/{sup 125}I uptake ratios in tissues indicative of loss of label from the chelate; for this reason, only 1B4M and MeO-DOTA were evaluated further. The {sup 177}Lu/{sup 125}I ratio in bone increased gradually with time for the chimeric conjugates; however, there were no significant differences between ch81C6-1B4M-DTPA-{sup 177}Lu and ch81C6-MeO-DOTA-{sup 177}Lu. In contrast, mu81C6-1B4M-DTPA-{sup 177}Lu and mu81C6-MeO-DOTA-{sup 177}Lu showed a more dramatic increase in the {sup 177}Lu/{sup 125}I ratio in bone - from 2.4{+-}0.3 and 1.7{+-}0.2 at Day 1 to 8.5{+-}1.1 and 4.2{+-}0.5 at Day 7, respectively. Conclusion: With these antitenascin constructs, the nature of the mAb had a profound influence on the relative degree of loss of {sup 177}Lu from these

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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)

  1. 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...

  2. 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.

  3. 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...

  4. 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

  5. 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...

  6. 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...

  7. Synthesis and Crystal Structure Determination of a Nickel(II Complex of an Acyclic Pentadentate (N5 Mono Schiff Base Ligand

    Directory of Open Access Journals (Sweden)

    R. V. Parish

    2001-10-01

    Full Text Available The asymmetrical tripodal tetraamine ligand N[(CH23NH2]2[(CH22NH2] (ppe was condensed with 2-acetylpyridine in the presence of nickel(II ion. In ethanolwater solution the reaction stops after the first stage of condensation, and a new nickel(II complex of an acyclic pentadentate (N5 mono Schiff base ligand was obtained. X-ray structure analysis of the resulting complex, [Ni(ppe-py(H2O](ClO42, indicates that condensation with 2-acetylpyridine is at the propylene chain of ppe. The geometry around the nickel ion is distorted octahedral in which the sixth co-ordination group is a solvent molecule.

  8. Isolation and Characterization of an Acyclic Isoprenoid from Semecarpus anacardium Linn. and its Antibacterial Potential in vitro - Antimicrobial Activity of Semecarpus anacardium Linn. Seeds -

    Directory of Open Access Journals (Sweden)

    Ayyakkannu Purushothaman

    2017-06-01

    Full Text Available Objectives: Semecarpus anacardium Linn. is a plant well-known for its antimicrobial, antidiabetic and anti-arthritic properties in the Ayurvedic and Siddha system of medicine. This has prompted the screening of this plant for antibacterial activity. The main aims of this study were to isolate compounds from the plant’s seeds and to evaluate their antibacterial effects on clinical bacterial test strains. Methods: The n-butanolic concentrate of the seed extract was subjected to thin layer chromatography (TLC and repeated silica gel column chromatography followed by elution with various solvents. The compound was identified based on observed spectral (IR, 1H NMR, 13C NMR and high-resolution mass spectrometry data. The well diffusion method was employed to evaluate the antibacterial activities of the isolated acyclic isoprenoid compound (final concentration: 5 - 15 μg/mL on four test bacterial strains, namely, Staphylococcus aureus (MTCC 96, Bacillus cereus

  9. Hydrothermal syntheses, characterizations and crystal structures of a new lead(II) carboxylate-phosphonate with a double layer structure and a new nickel(II) carboxylate-phosphonate containing a hydrogen-bonded 2D layer with intercalation of ethylenediamines

    International Nuclear Information System (INIS)

    Song, J.-L.; Mao, J.-G.; Sun, Y.-Q.; Zeng, H.-Y.; Kremer, R.K.; Clearfield, Abraham

    2004-01-01

    Hydrothermal reactions of N,N-bis(phosphonomethyl)aminoacetic acid (HO 2 CCH 2 N(CH 2 PO 3 H 2 ) 2 ) with metal(II) salts afforded two new metal carboxylate-phosphonates, namely, Pb 2 [O 2 CCH 2 N(CH 2 PO 3 )(CH 2 PO 3 H)]·H 2 O (1) and {NH 3 CH 2 CH 2 NH 3 }{Ni[O 2 CCH 2 N(CH 2 PO 3 H) 2 ](H 2 O) 2 } 2 (2). Among two unique lead(II) ions in the asymmetric unit of complex 1, one is five coordinated by five phosphonate oxygen atoms from 5 ligands, whereas the other one is five-coordinated by a tridentate chelating ligand (1 N and 2 phosphonate O atoms) and two phosphonate oxygen atoms from two other ligands. The carboxylate group of the ligand remains non-coordinated. The bridging of above two types of lead(II) ions through phosphonate groups resulted in a double layer with the carboxylate group of the ligand as a pendant group. These double layers are further interlinked via hydrogen bonds between the carboxylate groups into a 3D network. The nickel(II) ion in complex 2 is octahedrally coordinated by a tetradentate chelating ligand (two phosphonate oxygen atoms, one nitrogen and one carboxylate oxygen atoms) and two aqua ligands. These {Ni[O 2 CCH 2 N(CH 2 PO 3 H) 2 ][H 2 O] 2 } - anions are further interlinked via hydrogen bonds between non-coordinated phosphonate oxygen atoms to form a hydrogen bonded 2D layer. The 2H-protonated ethylenediamine cations are intercalated between two layers, forming hydrogen bonds with the non-coordinated carboxylate oxygen atoms. Results of magnetic measurements for complex 2 indicate that there is weak Curie-Weiss behavior with θ=-4.4 K indicating predominant antiferromagnetic interaction between the Ni(II) ions. Indication for magnetic low-dimension magnetism could not be detected

  10. An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes

    Energy Technology Data Exchange (ETDEWEB)

    Kiwamoto, R., E-mail: reiko.kiwamoto@wur.nl; Spenkelink, A.; Rietjens, I.M.C.M.; Punt, A.

    2015-01-01

    Acyclic α,β-unsaturated aldehydes present in food raise a concern because the α,β-unsaturated aldehyde moiety is considered a structural alert for genotoxicity. However, controversy remains on whether in vivo at realistic dietary exposure DNA adduct formation is significant. The aim of the present study was to develop physiologically based kinetic/dynamic (PBK/D) models to examine dose-dependent detoxification and DNA adduct formation of a group of 18 food-borne acyclic α,β-unsaturated aldehydes without 2- or 3-alkylation, and with no more than one conjugated double bond. Parameters for the PBK/D models were obtained using quantitative structure–activity relationships (QSARs) defined with a training set of six selected aldehydes. Using the QSARs, PBK/D models for the other 12 aldehydes were defined. Results revealed that DNA adduct formation in the liver increases with decreasing bulkiness of the molecule especially due to less efficient detoxification. 2-Propenal (acrolein) was identified to induce the highest DNA adduct levels. At realistic dietary intake, the predicted DNA adduct levels for all aldehydes were two orders of magnitude lower than endogenous background levels observed in disease free human liver, suggesting that for all 18 aldehydes DNA adduct formation is negligible at the relevant levels of dietary intake. The present study provides a proof of principle for the use of QSAR-based PBK/D modelling to facilitate group evaluations and read-across in risk assessment. - Highlights: • Physiologically based in silico models were made for 18 α,β-unsaturated aldehydes. • Kinetic parameters were determined by in vitro incubations and a QSAR approach. • DNA adduct formation was negligible at levels relevant for dietary intake. • The use of QSAR-based PBK/D modelling facilitates group evaluations and read-across.

  11. The supramolecular architecture of tris(naphthalene-1,5-diaminium) bis(5-aminonaphthalen-1-aminium) octakis[hydrogen (5-carboxypyridin-3-yl)phosphonate].

    Science.gov (United States)

    Wilk, Magdalena; Janczak, Jan; Videnova-Adrabinska, Veneta

    2012-09-01

    The asymmetric unit of the title compound, 3C(10)H(12)N(2)(2+)·2C(10)H(11)N(2)(+)·8C(6)H(5)NO(5)P(-), contains one and a half naphthalene-1,5-diaminium cations, in which the half-molecule has inversion symmetry, one 5-aminonaphthalen-1-aminium cation and four hydrogen (5-carboxypyridin-3-yl)phosphonate anions. The crystal structure is layered and consists of hydrogen-bonded anionic monolayers between which the cations are arranged. The acid monoanions are organized into one-dimensional chains along the [101] direction via hydrogen bonds established between the phosphonate sites. (C)O-H···N(py) hydrogen bonds (py is pyridine) crosslink the chains to form an undulating (010) monolayer. The cations serve both to balance the charge of the anionic network and to connect neighbouring layers via multiple hydrogen bonds to form a three-dimensional supramolecular architecture.

  12. 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...

  13. 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

  14. Synthesis of a Benzene-containing C1-Phosphonate Analogue of UDP-GlcNAc for the Inhibition of O-GlcNAc Transferase

    Energy Technology Data Exchange (ETDEWEB)

    Im, Jungkyun [Soonchunhyang Univ., Asan (Korea, Republic of)

    2016-01-15

    I report here the design, synthesis, and biological evaluation of a new C1-phosphonate analogue of UDP-GlcNAc as a potential inhibitor of OGT, an enzyme responsible for O-GlcNAc modification. The analogue was designed to mimic the transition state of the natural donor involved in the enzymatic reaction. However, the analogue showed somehow low activity as an inhibitor of OGT.

  15. Novel 2D or 3D alkaline-earth metal sulfonate-phosphonates based on [O 3S-C 2H 4-PO 3H] 2- ligand

    Science.gov (United States)

    Du, Zi-Yi; Wen, He-Rui; Xie, Yong-Rong

    2008-11-01

    Three novel alkaline-earth metal sulfonate-phosphonates based on [O 3S-C 2H 4-PO 3H] 2- ligand, namely, [Ca(O 3SC 2H 4PO 3H)(H 2O) 2] ( 1), [Sr(O 3SC 2H 4PO 3H)] ( 2) and [Ba 2(O 3SC 2H 4PO 3H) 2] ( 3), have been synthesized by hydrothermal reactions. They represent the first structurally characterized alkaline-earth metal complexes of phosphonic acid attached with a sulfonate group. The structure of compound 1 features a 2D layer based on 1D chains of [Ca 2(PO 3) 2] bridged by -CH 2-CH 2-SO 3- groups. Compounds 2 and 3 show pillar-layer architecture based on two different inorganic layers linked by -CH 2-CH 2- groups. The inorganic layer in compound 2 features a 1D chain of edge-sharing SrO 8 polyhedra whereas that in compound 3 features an edge-sharing Ba 2O 14 di-polyhedral unit which is further corner-shared with four neighboring ones. The [O 3S-C 2H 4-PO 3H] 2- ligand shows diverse coordination modes in the three alkaline-earth metal sulfonate-phosphonates.

  16. Corrosion protective performance of amino trimethylene phosphonic acid-metal complex layers fabricated on the cold-rolled steel substrate via one-step assembly

    Science.gov (United States)

    Yan, Ru; He, Wei; Zhai, Tianhua; Ma, Houyi

    2018-06-01

    Seeing that amino trimethylene phosphonic acid (ATMP) possesses very strong complexation ability to metal ions and the phosphonic acid group has good affinity for the oxidized iron surface, herein a simple and rapid film-forming method (one-step assembly method) was developed to construct the ATMP-Zn complex conversion layers (ATMP-Zn layers for short) on the cold-rolled steel (CRS) substrate. Zinc ions were found to participate in the formation process of ATMP-based composite film, which made the Zn-containing ATMP film significantly different in appearance, thickness, microstructure and film-forming mechanisms from the Zn-free ATMP film. There was mainly iron (ш) phosphonate in the Zn-free ATMP film, whereas there were Zn2+-ATMP complex and a certain amount of ZnO in the ATMP-Zn composite film. In addition, electrochemical test results clearly indicate that corrosion resistance of ATMP-Zn composite film was greatly enhanced due to the presence of Zn component. Moreover, the corrosion resistance performance could be controlled by adjusting film-forming time, pH and ATMP concentration in the film-forming solutions. The present study provides a new method for the design and fabrication of high-quality environmentally-friendly conversion layers.

  17. [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.

  18. 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

  19. 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)

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. Chirality- and pH-Controlled Supramolecular Isomerism in Cobalt Phosphonates and Its Impact on the Magnetic Behavior.

    Science.gov (United States)

    Feng, Jian-Shen; Bao, Song-Song; Ren, Min; Cai, Zhong-Sheng; Zheng, Li-Min

    2015-11-23

    Two pairs of enantiomeric compounds with formulas (S)- or (R)-Co3 (ppap)2 (4,4'-bpy)2 (H2 O)2 ⋅4 H2 O [(S)-1 or (R)-1], (S)- or (R)-Co3 (ppap)2 (4,4'-bpy)2 (H2 O)2 ⋅3 H2 O [(S)- or (R)-2), and related racemic compound Co3 (ppap)2 (4,4'-bpy)2 (H2 O)2 ⋅4 H2 O (rac-3; 4,4'-bpy=4,4'-bipyridine, H3 ppap=3-phenyl-2-[(phosphonomethyl)amino]propanoic acid) are reported. Compounds 1 and rac-3 show identical three-dimensional framework structures, whereas compounds 2 have two-dimensional layer structures. Compounds 1 and 2 are catenation isomers, formation of which is controlled solely by the pH of the reaction mixtures, whereas the formation of isomeric compounds 1 and rac-3 is controlled purely by the chirality of the phosphonate ligand. The magnetic properties of fully dehydrated (S)-1, (S)-2, and rac-3 are highly dependent on both structure and chirality. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Tribology and stability of organic monolayers on CrN: a comparison among silane, phosphonate, alkene, and alkyne chemistries.

    Science.gov (United States)

    Pujari, Sidharam P; Li, Yan; Regeling, Remco; Zuilhof, Han

    2013-08-20

    The fabrication of chemically and mechanically stable monolayers on the surfaces of various inorganic hard materials is crucial to the development of biomedical/electronic devices. In this Article, monolayers based on the reactivity of silane, phosphonate, 1-alkene, and 1-alkyne moieties were obtained on the hydroxyl-terminated chromium nitride surface. Their chemical stability and tribology were systematically investigated. The chemical stability of the modified CrN surfaces was tested in aqueous media at 60 °C at pH 3, 7, and 11 and monitored by static water contact angle measurements, X-ray photoelectron spectroscopy (XPS), ellipsometry, and Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS). The tribological properties of the resulting organic monolayers with different end groups (fluorinated or nonfluorinated) were studied using atomic force microscopy (AFM). It was found that the fluorinated monolayers exhibit a dramatic reduction of adhesion and friction force as well as excellent wear resistance compared to those of nonfluorinated coatings and bare CrN substrates. The combination of remarkable chemical stability and superior tribological properties makes these fluorinated monolayers promising candidates for the development of robust high-performance devices.

  8. In Situ Investigation of the Adsorption of Styrene Phosphonic Acid on Cassiterite (110 Surface by Molecular Modeling

    Directory of Open Access Journals (Sweden)

    Guichen Gong

    2017-09-01

    Full Text Available Abstract: The flotation, adsorption and bonding mechanisms of styrene phosphonic acid (SPA to cassiterite were studied using microflotation tests, zeta potential measurements, solution chemistry analysis and density functional theory (DFT calculations in this paper. Flotation results demonstrated SPA was an excellent collector for cassiterite which could recover over 85% cassiterite particles with the pH range 4.3–6.06 and 40 mg/L SPA. Zeta potential measurements and solution chemistry analysis revealed the adsorption of SPA was mainly contributed by the chemisorption of the monoanions on cassiterite surfaces. Frontier molecular orbital theory analysis and adsorption energy calculation results proved the monoanion of SPA was able to replace the OH− on cassiterite surfaces. The adsorption structure optimization results confirmed the binuclear complex was the most favorable adsorption configuration of SPA on cassiterite (110 surface. Mulliken population calculations and density of states analysis indicated during the bonding process the Sn3 atom lost electrons to O3 atom, and the bonding interaction between O3 and Sn3 atoms was mainly from the contribution of the 2p orbital of O3 atom and the 5s and 5p orbitals of Sn3 atom.

  9. Studies of the influence of different anions on extraction of neodymium with di(1-methylheptyl)methyl phosphonate

    International Nuclear Information System (INIS)

    Chun-Hui Huang; Rong-Fang Xi; Hai Guo; Guang-Xian Xu

    1988-01-01

    A study was made on extraction of Nd(NCS) 3 , Nd(ClO 4 ) 3 , Nd(NO 3 ) 3 by di-(1-methylhexyl)methyl phosphonate (P-350) in hexane. ΔG 0 (kJ/mol), ΔH 0 (kJ/mol) and ΔS 0 (kJ/mol) were calculated. They are equal to: -9.719, -29.92, -67.78 for P-350(hexane)-Nd(NCS) 3 system; 3.752, -74.31, -261.9 for P-350((hexane)-Nd(ClO 4 ) 3 system; 2.265, -22.69, -83.68 for P-350(hexane)-Nd(NO 3 ) 3 system. Structure of extracted complexes in hexane solution and corresponding solid complexes were correlated with triphenylphosphine oxide as P-350 model. Data of IR-spectroscopy show, that absorption bands of complexes in saturated organic solvents or in the solid phase are shifted to the region of lower frequencies as compared to absorption bands of corresponding salts. This testifies to similarity of complex structures in both phases

  10. New N-Acetyltransferase Fold in the Structure and Mechanism of the Phosphonate Biosynthetic Enzyme FrbF

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Brian; Cobb, Ryan E.; DeSieno, Matthew A.; Zhao, Huimin; Nair, Satish K. (UIUC)

    2015-10-15

    The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 {angstrom} resolution crystal structure of FrbF in complex with acetyl-CoA, which demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure to guide structure-function studies that identified the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provide a molecular framework toward the production of novel N-acyl derivatives of FR-900098.

  11. Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

    International Nuclear Information System (INIS)

    Essman, Stephanie C.; Lewis, Michael R.; Fox, Derek B.

    2008-01-01

    Introduction: Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate ( 153 Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic 153 Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of 153 Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of 153 Sm-EDTMP on growth of long bones. Methods: Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of 153 Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P 153 Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted

  12. Phosphonate self-assembled monolayers as organic linkers in solid-state quantum dot sensetized solar cells

    KAUST Repository

    Ardalan, Pendar

    2010-06-01

    We have employed X-ray photoelectron spectroscopy (XPS), ultraviolet-visible (UV-vis) spectroscopy, infrared (IR) spectroscopy, water contact angle (WCA) measurements, ellipsometry, and electrical measurements to study the effects of self-assembled monolayers (SAMs) with phosphonic acid headgroups on the bonding and performance of cadmium sulfide (CdS) solid-state quantum dot sensitized solar cells (QDSSCs). ∼2 to ∼6 nm size CdS quantum dots (QDs) were grown on the SAM-passivated TiO2 surfaces by successive ionic layer adsorption and reaction (SILAR). Our results show differences in the bonding of the CdS QDs at the TiO2 surfaces with a SAM linker. Moreover, our data indicate that presence of a SAM increases the CdS uptake on TiO2 as well as the performance of the resulting devices. Importantly, we observe ∼2 times higher power conversion efficiencies in the devices with a SAM compared to those that lack a SAM. © 2010 IEEE.

  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. 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...

  15. 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.

  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. 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.

  1. 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.

  2. 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.

  3. 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)

  4. 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

  5. The resolution of acyclic P-stereogenic phosphine oxides via the formation of diastereomeric complexes: A case study on ethyl-(2-methylphenyl)-phenylphosphine oxide.

    Science.gov (United States)

    Bagi, Péter; Varga, Bence; Szilágyi, András; Karaghiosoff, Konstantin; Czugler, Mátyás; Fogassy, Elemér; Keglevich, György

    2018-04-01

    As an example of acyclic P-chiral phosphine oxides, the resolution of ethyl-(2-methylphenyl)-phenylphosphine oxide was elaborated with TADDOL derivatives, or with calcium salts of the tartaric acid derivatives. Besides the study on the resolving agents, several purification methods were developed in order to prepare enantiopure ethyl-(2-methylphenyl)-phenylphosphine oxide. It was found that the title phosphine oxide is a racemic crystal-forming compound, and the recrystallization of the enantiomeric mixtures could be used for the preparation of pure enantiomers. According to our best method, the (R)-ethyl-(2-methylphenyl)-phenylphosphine oxide could be obtained with an enantiomeric excess of 99% and in a yield of 47%. Complete racemization of the enantiomerically enriched phosphine oxide could be accomplished via the formation of a chlorophosphonium salt. Characterization of the crystal structures of the enantiopure phosphine oxide was complemented with that of the diastereomeric intermediate. X-ray analysis revealed the main nonbonding interactions responsible for enantiomeric recognition. © 2018 Wiley Periodicals, Inc.

  6. Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R- and (S-aminopropanediol as an acyclic linker

    Directory of Open Access Journals (Sweden)

    Daniel Lachmann

    2010-02-01

    Full Text Available The Nile Blue chromophore was incorporated into oligonucleotides using “click” chemistry for the postsynthetic modification of oligonucleotides. These were synthesized using DNA building block 3 bearing an alkyne group and reacted with the azide 4. (R-3-amino-1,2-propanediol was applied as the linker between the phosphodiester bridges. Two sets of DNA duplexes were prepared. One set carried the chromophore in an A-T environment, the second set in a G-C environment. Both were characterized by optical spectroscopy. Sequence-dependent fluorescence quenching was applied as a sensitive tool to compare the stacking interactions with respect to the chirality of the acyclic linker attachment. The results were compared to recent results from duplexes that carried the Nile Blue label in a sequentially and structurally identical context, except for the opposite chirality of the linker ((S-3-amino-1,2-propandiol. Only minor, negligible differences were observed. Melting temperatures, UV–vis absorption spectra together with fluorescence quenching data indicate that Nile Blue stacks perfectly between the adjacent base pairs regardless of whether it has been attached via an S- or R-configured linker. This result was supported by geometrically optimized DNA models.

  7. Synthesis, kinetic evaluation, and utilization of a biotinylated dipeptide proline diphenyl phosphonate for the disclosure of dipeptidyl peptidase IV-like serine proteases.

    Science.gov (United States)

    Gilmore, Brendan F; Carson, Louise; McShane, Laura L; Quinn, Derek; Coulter, Wilson A; Walker, Brian

    2006-08-18

    In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.

  8. Crystal structure and characterization of a novel layered copper-lithium phosphonate with antiferromagnetic intrachain Cu(II)···Cu(II) interactions

    Energy Technology Data Exchange (ETDEWEB)

    Abdelbaky, Mohammed S.M. [Departments of Physical and Analytical Chemistry and Organic and Inorganic Chemistry, University of Oviedo-CINN, 33006 Oviedo (Spain); Amghouz, Zakariae [Scientific and Technical Services, University of Oviedo-CINN, 33006 Oviedo (Spain); Department of Materials Science and Metallurgical Engineering, University of Oviedo, Campus Universitario, 33203 Gijón (Spain); Blanco, David Martínez [Scientific and Technical Services, University of Oviedo-CINN, 33006 Oviedo (Spain); García-Granda, Santiago; García, José R. [Departments of Physical and Analytical Chemistry and Organic and Inorganic Chemistry, University of Oviedo-CINN, 33006 Oviedo (Spain)

    2017-04-15

    Novel metal phosphonate [CuLi(PPA)] [H{sub 3}PPA=3-phosphonopropionic acid] was synthesized hydrothermally and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. It crystallizes in the space group C2/c, with cell parameters a=21.617(2) Å, b=4.9269(2) Å, c=14.342(1) Å, β=132.3(2)°, and Z=8. Its framework is built up from a main trimer, acting as a secondary building unit (SBU), which is formed by vertex-shared between two (LiO{sub 4}) and one (Cu(1)O{sub 4}) polyhedra. These units repeat along b-axis forming infinite inorganic chains, these chains are in turn cross-linked by corner sharing with (Cu(2)O{sub 4}) polyhedra to produce inorganic layers lying in the bc-plane. The neighboring layers are connected through the PPA ligand, leading to a 3D pillared-layered structure. The topological analysis reveals that the compound exhibits 3,4,10-c net. Finally, magnetic susceptibility measurement of this compound over the temperature range of 2–300 K reveals the occurrence of weak antiferromagnetic intrachain interactions. - Graphical abstract: Hydrothermal synthesis and structural characterization of a novel lithium-copper phosphonate, formulated as [CuLi(PPA)] (H{sub 3}PPA=3-phosphonopropionic acid), have been reported. This compound has a 3D pillared-layered structure with 3,4,10-c net topology. The magnetic susceptibility data over the temperature range of 2–300 K reveals the occurrence of weak antiferromagnetic interactions. - Highlights: • Novel metal phosphonate, [CuLi(PPA)] (1), has been synthesized and characterized. • Compound 1 has a 3D pillared-layered structure with 3,4,10-c net topology. • Magnetic susceptibility data reveals the occurrence of weak antiferromagnetic interactions.

  9. Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Essman, Stephanie C. [Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States)], E-mail: essmans@missouri.edu; Lewis, Michael R. [Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri-Columbia, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Fox, Derek B. [Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States)

    2008-02-15

    Introduction: Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate ({sup 153}Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic {sup 153}Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of {sup 153}Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of {sup 153}Sm-EDTMP on growth of long bones. Methods: Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of {sup 153}Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P<.05. Results: Significant differences in lengths of multiple bones were detected between the high-dose group and other treatment groups and controls at each time interval. A significant difference in lengths of the tibias was also noted in the medium-treatment group, compared to controls. Mean reduction of bone length was first detected at 4 months and did not increase significantly over time. Conclusions: These data suggest that clinically significant bone shortening may occur as a result of high-dosage administration of {sup 153}Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted.

  10. Phosphonic acids aid composition adjustment in the synthesis of Cu_2_+_xZn_1_−_xSnSe_4_−_y nanoparticles

    International Nuclear Information System (INIS)

    Ibáñez, Maria; Berestok, Taisiia; Dobrozhan, Oleksandr; LaLonde, Aaron; Izquierdo-Roca, Victor; Shavel, Alexey; Pérez-Rodríguez, Alejandro; Snyder, G. Jeffrey; Cabot, Andreu

    2016-01-01

    The functional properties of quaternary I_2–II–IV–VI_4 nanomaterials, with potential interest in various technological fields, are highly sensitive to compositional variations, which is a challenging parameter to adjust. Here we demonstrate the presence of phosphonic acids to aid controlling the reactivity of the II element monomer to be incorporated in quaternary Cu_2ZnSnSe_4 nanoparticles and thus to provide a more reliable way to adjust the final nanoparticle metal ratios. Furthermore, we demonstrate the composition control in such multivalence nanoparticles to allow modifying charge carrier concentrations in nanomaterials produced from the assembly of these building blocks.

  11. 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.

  12. 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

  13. 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°

  14. 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)

  15. 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

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Pitting corrosion of copper in aqueous solutions containing phosphonic acid as an inhibitor. Hosuhon san wo inhibita toshite fukumu suiyoekichu ni okeru do no koshiku ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Y. (Muroran Univ., Hokkaido (Japan). Graduate School); Seri, O.; Tagashira, K. (Muroran Univ., Hokkaido (Japan)); Nagata, K. (Sumitomo Light Metal Co. Ltd., Tokyo (Japan). Technical Research Lab.)

    1993-09-15

    Phosphonic acid-based inhibitors that are poured into cooling water for copper-tube circulation systems for open heat-accumulators were studied on their influence on pitting corrosion of copper. Amino trimethylene phosphonic acid (ATMP) dissolved into distilled water to 50 ppm was used for the immersion corrosion test. The corrosion-proof effect of additives such as ZnSO4, benzotriazole (BTA) was tested too. 0.5 mm thick phosphate-treated copper plates with a hole of 5 mm in diameter were used as test specimens. Pitting corrosion on the copper plate occurred when ATMP, BTA and ZnSO4 coexisted. It was proved that SO4 [sup 2-] is essential since Na2SO4 in stead of ZnSO4 induced also corrosion. The pitting took place when 0.6 ppm or more of SO4 [sup 2-] was present in a BTA-added ATMP solution. It was observed that the pitting is prone to occur with increase of SO4 [sup 2-] and the number of pitting increases. The following relationship is established when pitting corrosion occurs; E[sub b] [le] E[sub corr], where the former is a potential value at which current density shows a steep increase and the latter is an average value of spontaneous electrode potential showing a plateau. 8 refs., 11 figs., 1 tab.

  4. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    Science.gov (United States)

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-07

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.

  5. Recovery of phosphonate surface contaminants from glass using a simple vacuum extractor with a solid-phase microextraction fiber

    International Nuclear Information System (INIS)

    Groenewold, Gary S.; Scott, Jill R.; Rae, Catherine

    2011-01-01

    operational equilibrium is being approached. Fractional recovery decreased with increasing time between exposure and sampling; however, recordable quantities of the phosphonates could be collected three weeks after exposure.

  6. Structures and Spectroscopy Studies of Two M(II-Phosphonate Coordination Polymers Based on Alkaline Earth Metals (M = Ba, Mg

    Directory of Open Access Journals (Sweden)

    Kui-Rong Ma

    2013-01-01

    Full Text Available The two examples of alkaline-earth M(II-phosphonate coordination polymers, [Ba2(L(H2O9]·3H2O (1 and [Mg1.5(H2O9]·(L-H21.5·6H2O (2 (H4L = H2O3PCH2N(C4H8NCH2PO3H2, N,N′-piperazinebis(methylenephosphonic acid, (L-H2 = O3PH2CHN(C4H8NHCH2PO3 have been hydrothermally synthesized and characterized by elemental analysis, FT-IR, PXRD, TG-DSC, and single-crystal X-ray diffraction. Compound 1 possesses a 2D inorganic-organic alternate arrangement layer structure built from 1D inorganic chains through the piperazine bridge, in which the ligand L−4 shows two types of coordination modes reported rarely at the same time. In 1, both crystallographic distinct Ba(1 and Ba(2 ions adopt 8-coordination two caps and 9-coordination three caps triangular prism geometry structures, respectively. Compound 2 possesses a zero-dimensional mononuclear structure with two crystallographic distinct Mg(II ions. Free metal cations   [MgO6]n2+ and uncoordinated anions (L-H2n2- are joined together by static electric force. Results of photoluminescent measurement indicate three main emission bands centered at 300 nm, 378.5 nm, and 433 nm for 1 and 302 nm, 378 nm, and 434.5 nm for 2 (λex=235 nm, respectively. The high energy emissions could be derived from the intraligand π∗-n transition stations of H4L (310 nm and 382 nm, λex=235 nm, while the low energy emission (>400 nm of 1-2 may be due to the coordination effect with metal(II ions.

  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

    2013-02-15

    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.

  8. 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

  9. 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.

  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. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.)

  5. 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.

  6. 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

  7. 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...

  8. 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.

  9. 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

  10. 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)

  11. 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.

  12. 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.

  13. Increasing the Fill Factor of Inverted P3HT:PCBM Solar Cells Through Surface Modification of Al-Doped ZnO via Phosphonic Acid-Anchored C60 SAMs

    DEFF Research Database (Denmark)

    Stubhan, Tobias; Salinas, Michael; Ebel, Alexander

    2012-01-01

    The influence of aluminum-doped zinc oxide (AZO) electron extraction layers modified with self-assembled monolayers (SAMs) on inverted polymer solar cells is investigated. It is found that AZO modification with phosphonic acid-anchored Fullerene–SAMs leads to a reduction of the series resistance,...

  14. Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: comparison with structures of other complexes.

    Science.gov (United States)

    Kim, H; Lipscomb, W N

    1990-06-12

    O-[[(1R)-[[N-(Phenylmethoxycarbonyl)-L-alanyl]amino]ethyl] hydroxyphosphinyl]-L-3-phenyllacetate [ZAAP(O)F], an analogue of (benzyloxycarbonyl)-Ala-Ala-Phe or (benzyloxycarbonyl)-Ala-Ala-phenyllactate, binds to carboxypeptidase A with great affinity (Ki = 3 pM). Similar phosphonates have been shown to be transition-state analogues of the CPA-catalyzed hydrolysis [Hanson, J. E., Kaplan, A. P., & Bartlett, P. A. (1989) Biochemistry 28, 6294-6305]. In the present study, the structure of the complex of this phosphonate with carboxypeptidase A has been determined by X-ray crystallography to a resolution of 2.0 A. The complex crystallizes in the space group P2(1)2(1)2(1) with cell dimensions a = 61.9 A, b = 67.2 A, and c = 76.2 A. The structure of the complex was solved by molecular replacement. Refinement of the structure against 20,776 unique reflections between 10.0 and 2.0 A yields a crystallographic residual of 0.193, including 140 water molecules. The two phosphinyl oxygens of the inhibitor bind to the active-site zinc at 2.2 A on the electrophilic (Arg-127) side and 3.1 A on the nucleophilic (Glu-270) side. Various features of the binding mode of this phosphonate inhibitor are consistent with the hypothesis that carboxypeptidase A catalyzed hydrolysis proceeds through a general-base mechanism in which the carbonyl carbon of the substrate is attacked by Zn-hydroxyl (or Zn-water). An unexpected feature of the bound inhibitor, the cis carbamoyl ester bond at the benzyloxycarbonyl linkage to alanine, allows the benzyloxycarbonyl phenyl ring of the inhibitor to interact favorably with Tyr-198. This complex structure is compared with previous structures of carboxypeptidase A, including the complexes with the potato inhibitor, a hydrated keto methylene substrate analogue, and a phosphonamidate inhibitor. Comparisons are also made with the complexes of thermolysin with some phosphonamidate inhibitors.

  15. 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

  16. 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.

  17. 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

  18. 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)

  19. 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)

  20. 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.