DOCSLIB.ORG

Chemicalsynthesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemicalsynthesis CHEMICAL SYNTHESIS, DISPOSITION AND METABOLISM OF DOPAMINE AND NORADRENALINE SULPHATES BARBARA ALEKSANDRA OSIKOWSKA A thesis submitted for the degree of Doctor of Philosophy to the University of London December 1983 - 2- ABSTRACT The existence of an enzymatic pathway which is capable of sulphating the catecholamine neurotransmitters has been known for over four decades. The importance of this metabolic pathway and its overall contribution to the enzymatic breakdown of these neurotransmitters has generally received less attention than deamination and JKmethylation. The aim of this work was to synthesise authentic dopamine and noradrenaline ^-sulphates, for use as standards in studies on the disposition and metabolism of these important products of dopamine and noradrenaline metabolism. 1. Three products resulted from chemical sulphonation of dopamine: dopamine 3-0-sulphate, dopamine 4-0-sulphate and dopamine 6- s u l p h o n i c acid. 2. Because all three products of dopamine sulphonation are isomeric, chemically similar organic acids and could not be distinguished by analytical techiques such as elemental analysis, ultraviolet spectroscopy and infrared spectroscopy, high performance liquid chromatography was employed for the separation and purification of these products, and nuclear magnetic resonance spectroscopy was considered to be the only technique powerful enough to distinguish between these isomers. 3. Noradrenaline 3- and 4-0-sulphates were isolated from a one-step synthetic reaction. They were separated, purified and characterised using techniques applied for the synthesis and separation of dopamine ^-sulphates. - 3- 4. The disposition of dopamine 3- and 4-0-sulphates was investigated in human urine before and following L-dopa administration and in multiple urine samples from a single subject. Both dopamine O-sulphates were present in urine under physiological conditions and after L-dopa; however, dopamine 3-0-sulphate was the major urinary conjugate in both circumstances. 5. The disposition of dopamine and noradrenaline 3- and 4-0-sulphates were investigated in rabbit brain, heart, kidney, liver, spleen and small intestine. Dopamine O-sulphates were not detected in any of the tissues with the method of analysis used; both noradrenaline O^-sulphate isomers were present in the above tissues in ratios depending on the animal and tissue investigated. In tissue homogenates of one rabbit, noradrenaline 4-0-sulphate was not detected. 6. Experiments investigating the in vitro metabolism of dopamine and noradrenaline O-sulphates showed that the aforementioned compounds were substrates for dopamine 3 -hydroxylase, the enzyme responsible for the conversion of dopamine to noradrenaline. Two products were formed following incubation of dopamine 3 -hydroxylase with dopamine O-sulphates, namely free noradrenaline and noradrenaline ()-sulphates. In the presence of active dopamine 3 -hydroxylase in the reaction mixture noradrenaline O-sulphates yielded free noradrenaline. The effects of a dopamine 3 -hydroxylase inhibitor on the above reactions were also investigated. 7. Observations in both experimental animals and man suggest that there may be important interindividual variations in the extent of 4-0- sulphation of these amines, the underlying basis for which cannot at present be explained. - 4- ACKNOWLEDGEMENTS I would like to thank all those whose help in this project made its completion possible. I am grateful to Professors P.S. Sever and W.S. Peart for allowing me to carry out this work in their departments. Professor P.S. Sever and Dr. J. Idle provided help, new ideas, continuous encouragement, criticism and friendship. Dr. F Swinbourne assisted in providing facilities for nuclear magnetic resonance spectroscopy and helped in the interpretation of the spectra. I would also like to express my thanks to the following: Mr. R. Mattin for his technical assistance, Miss G. Bartlett for typing the thesis and Drs. R. Unwin and S. Thom for proof-reading. I am grateful to all my friends at St. Mary's Hospital Medical School, past and present, whose friendship and encouragement allowed the satisfactory completion of this thesis. The work was generously supported by the Wellcome Trust. I reserve final thanks for my husband and my parents, whose support and understanding given freely through the duration of this work I could never fully return. - 5- CONTENTS P a g e ABBREVIATIONS 6 LIST OF TABLES 7 LIST OF FIGURES 9 CHAPTER: INTRODUCTION ...12 2 STUDIES ON THE CHEMICAL SULPHONATION OF DOPAMINE AND NORADRENALINE ... 52 3 DISPOSITION OF DOPAMINE O-SULPHATES IN HUMAN URINE 98 4 DISPOSITION OF NORADRENALINE 3- AND 4-0- SULPHATES IN RABBIT TISSUES ... 116 5 FURTHER METABOLISM OF DOPAMINE AND NORADRENALINE SULPHATES ... 137 6 DISCUSSION AND CONCLUDING REMARKS ... 166 BIBLIOGRAPHY ... 183 RELEVANT PUBLICATIONS ...212 ABBREVIATIONS COMT catechol ()-methyl transferase DA d o p a m i n e DA 3 - 0 - S 0 4 dopamine 3-0-sulphate DA 4-0-S0. dopamine 4-0-sulphate - 4 DBH d o p a m i n e 3 -hydroxylase DHP 6 3,4-dihydroxyphenylglycol d o p a d i hydroxyphenylalan i ne DOPAC dihydroxyphenylacetic acid h . p . 1.c. high performance liquid chromatography I.R. infrared MAO monoamine oxidase MHPG 3-methoxy-4-hydroxyphenylglycol NA noradrenaline N A 3 - 0 - S 0 4 noradrenaline 3-0-sulphate N A 4 - 0 - S 0 4 noradrenaline 4-0-sulphate n.m.r. nuclear magnetic resonance PAP 3'-phosphoadenosine-5'-phosphate PAPS 3 ‘-phosphoadenosine-5'-phosphosulphate PNMT phenylethanolamine-Tf-methyltransferase PP. inorganic phosphate l PST phenolsulphotransferase S.D. standard deviation U.V. ultraviolet VMA 4-hydroxy-3-methoxymandelic acid - 7- LIST OF TABLES 1.1 Plasma catecholamines (pg/ml) ...24 1.2 Percentage increment in plasma noradrenaline and adrenaline with various stimuli ... 28 2.1 Products of reactions of various sulphonating agents with dopamine at various temperatures ... 65 2.2 Products of sulphonation of noradrenaline with H^SO^ at various temperatures and time intervals 79 2.3 Products of reaction of chlorosulphonic acid with noradrenaline at various time intervals 83 2.4 Products of reaction of chlorosulphonic acid with noradrenaline: effect of varying reaction mixture composition ... 85 3.1 Dopamine 0-sulphate content in urine under physiological conditions ... 106 3.2 Dopamine ^-sulphate isomers in urine following oral administration of L-dopa (0.5 g) ... Ill 3.3 Recovery of orally administered L-dopa (0.5 g) in 24 h urine as dopamine 3- and 4-0-sulphates ... 112 4.1 Noradrenaline 3- and 4-0-sulphates in rabbit brain tissue ... 121 4.2 Noradrenaline 3- and 4-0-sulphates in rabbit heart tissue ... 123 4.3 Noradrenaline 3- and 4-0-sulphates in rabbit kidney tissue ... 125 4.4 Noradrenaline 3- and 4-0-sulphates in rabbit spleen tissue ...127 Noradrenaline 3- and 4-0-sulphates in rabbit liver tissue 129 Noradrenaline 3- and 4-0-sulphates in rabbit small intestine tissue 131 Dopamine 4-0-sulphate incubation with D$H at different time intervals 146 Dopamine 3-0-sulphate incubation with D$H at different time intervals 147 Kinetic study of D$H with dopamine as the s u b s t r a t e 147 Kinetic study of D$H with dopamine 4-0-sulphate as the substrate 149 Concentrations of free noradrenaline formed during incubation of dopamine 4-0-sulphate with D3H in the absence or presence of fusaric acid 151 Products formed by the incubation of dopamine 4-0- sulphate with Df3H 152 Kinetic study of DBH with dopamine 3-0-sulphate as the substrate 153 Concentrations of free noradrenaline formed during incubation of dopamine 3-0-sulphate with DBH in the absence or presence of fusaric acid 155 Products formed by the incubation of dopamine 3-0- sulphate with D^H 156 Noradrenaline 4-0-sulphate incubation in the p r e s e n c e of active D$H ... ... Noradrenaline 3-0-sulphate incubation in the presence of active D&H - 9- L1ST OF FIGURES 1.1 The biosynthesis of dopamine, noradrenaline and a d r e n a l i n e 15 1.2 Metabolic routes of dopamine, noradrenaline and a d r e n a l i n e 20 2.1 Products of chemical sulphonation of dopamine 67 2.2 H.p.l.c. chromatogram of products formed during chemical sulphonation of dopamine ... 68 2.3 250 MHz *H n.m.r. spectrum (aromatic region) of dopamine 6-sulphonic acid (product I, bottom), including expanded spectrum (top) ... 71 13 2.4 Off-resonance decoupled C n.m.r. spectrum of d o p a m i n e 6-sulphonic acid 72 2.5 250 MHz n.m.r. spectrum of dopamine 4-0- sulphate (product II) 75 2.6 250 MHz *H n.m.r. spectrum of dopamine 3-0- sulphate (product III) 77 2.7 Products of chemical sulphonation of noradrenaline 88 2.8 H.p.l.c. chromatogram of products formed during chemical sulphonation of noradrenaline by chlorosulphonic acid 89 2.9 250 MHz *H n.m.r. spectrum of noradrenaline 4-0- sulphate (product I) 91 2.10 250 MHz ^H n.m.r. spectrum of noradrenaline 3-0- sulphate (product II) 93 3.1 Standard curve for the estimation of dopamine 3- and 4-0-sulphates 105 H.p.l.c. chromatogram of dopamine £-sulphate s t a n d a r d s 107 H.p.l.c. chromatogram of normal urine containing both dopamine 0- s u l p h a t e s 108 H.p.l.c. chromatogram of urine after L-dopa administration, for estimation of dopamine 4-0- sulphate content 109 H.p.l.c. chromatogram of urine p r e s e n t e d in Fig. 3.4, appropriately i iluted for estimation of 3-0-sulphate content • • • • • • 110 H.p.l.c. chromatogram of authentic noradrenaline 3- and 4-0-sulphates • • • • • • 120 H.p.l.c.
Load more

Recommended publications
  • Transfer of Pseudomonas Plantarii and Pseudomonas Glumae to Burkholderia As Burkholderia Spp
    INTERNATIONALJOURNAL OF SYSTEMATICBACTERIOLOGY, Apr. 1994, p. 235-245 Vol. 44, No. 2 0020-7713/94/$04.00+0 Copyright 0 1994, International Union of Microbiological Societies Transfer of Pseudomonas plantarii and Pseudomonas glumae to Burkholderia as Burkholderia spp. and Description of Burkholderia vandii sp. nov. TEIZI URAKAMI, ’ * CHIEKO ITO-YOSHIDA,’ HISAYA ARAKI,’ TOSHIO KIJIMA,3 KEN-ICHIRO SUZUKI,4 AND MU0KOMAGATA’T Biochemicals Division, Mitsubishi Gas Chemical Co., Shibaura, Minato-ku, Tokyo 105, Niigata Research Laboratory, Mitsubishi Gas Chemical Co., Tayuhama, Niigatu 950-31, ’Plant Pathological Division of Biotechnology, Tochigi Agricultural Experiment Station, Utsunomiya 320, Japan Collection of Microorganisms, The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-01,4 and Institute of Molecular Cell and Biology, The University of Tokyo, Bunkyo-ku, Tokyo 113,’ Japan Plant-associated bacteria were characterized and are discussed in relation to authentic members of the genus Pseudomonas sensu stricto. Bacteria belonging to Pseudomonas rRNA group I1 are separated clearly from members of the genus Pseudomonas sensu stricto (Pseudomonasfluorescens rRNA group) on the basis of plant association characteristics, chemotaxonomic characteristics, DNA-DNA hybridization data, rRNA-DNA hy- bridization data, and the sequences of 5s and 16s rRNAs. The transfer of Pseudomonas cepacia, Pseudomonas mallei, Pseudomonas pseudomallei, Pseudomonas caryophylli, Pseudomonas gladioli, Pseudomonas pickettii, and Pseudomonas solanacearum to the new genus Burkholderia is supported; we also propose that Pseudomonas plantarii and Pseudomonas glumae should be transferred to the genus Burkholderia. Isolate VA-1316T (T = type strain) was distinguished from Burkholderia species on the basis of physiological characteristics and DNA-DNA hybridization data. A new species, Burkholderia vandii sp.
    [Show full text]
  • JPET #212357 1 TITLE PAGE Effects of Pharmacologic Dopamine Β
    JPET Fast Forward. Published on May 9, 2014 as DOI: 10.1124/jpet.113.212357 JPETThis Fast article Forward. has not been Published copyedited and on formatted. May 9, The 2014 final as version DOI:10.1124/jpet.113.212357 may differ from this version. JPET #212357 TITLE PAGE Effects of Pharmacologic Dopamine β-Hydroxylase Inhibition on Cocaine-Induced Reinstatement and Dopamine Neurochemistry in Squirrel Monkeys Debra A. Cooper, Heather L. Kimmel, Daniel F. Manvich, Karl T. Schmidt, David Weinshenker, Leonard L. Howell Yerkes National Primate Research Center Division of Neuropharmacology and Neurologic Diseases (D.A.C., H.L.K., L.L.H.), Department of Pharmacology (H.L.K., L.L.H.), Department of Human Genetics (D.A.C., D.F.M, K.T.S., D.W.), and Department of Psychiatry and Behavioral Sciences (L.L.H.) Emory University, Atlanta, Georgia Downloaded from jpet.aspetjournals.org at ASPET Journals on September 24, 2021 1 Copyright 2014 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on May 9, 2014 as DOI: 10.1124/jpet.113.212357 This article has not been copyedited and formatted. The final version may differ from this version. JPET #212357 RUNNING TITLE PAGE Running Title: Effects of Dopamine β-Hydroxylase Inhibition in Monkeys Correspondence: Dr LL Howell, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA, Tel: +1 404 727 7786; Fax: +1 404 727 1266; E- mail: [email protected] Text Pages: 19 # Tables: 1 # Figures: 5 # References: 51 Abstract: 250 words Introduction: 420 words Discussion: 1438 words Downloaded from Abbreviations aCSF artificial cerebrospinal fluid DA dopamine jpet.aspetjournals.org DBH dopamine β-hydroxylase EDMax maximally-effective unit dose of cocaine (self-administration) EDPeak maximally-effective dose of pre-session drug prime (reinstatement) at ASPET Journals on September 24, 2021 FI fixed-interval FR fixed-ratio HPLC high-performance liquid chromatography i.m.
    [Show full text]
  • Effects of Inhibitors of Catecholamine-Synthesizing Enzymes on the Mouse Adrenal Medulla
    ACTA HISTOCHEM. CYTOCHEM. Vol. 5 No. 2, 1972 EFFECTS OF INHIBITORS OF CATECHOLAMINE- SYNTHESIZING ENZYMES ON THE MOUSE ADRENAL MEDULLA IKUKO NAGATSU, YUMIKO SOTOKAWA* and MASAO SANO * Department of Anatomy and Physiology, Aichi Prefectural Collegeof Nursing, ands Department of Anatomy, School of Dentistry, Aichi-Gakuin University, Nagoya Received for publication March 16, 1972 Oudenone (a tyrosine hydroxylase inhibitor) and fusaric acid (a dopamine- β-hydroxylase inhibitor) had some effects on fine structures of the adrenal medulla. The Golgi apparatus was not seen to be well developed, and the formation of epinephrine and norepinephrine granules appeared to be dec- reased. The limiting membrane of norepinephrine granules showed a ten- dency of fusing each other, and the density of epinephrine granules was seen to be decreased. Both epinephrine and norepinephrine granules showed a reduction in size of their dense core. It is concluded that oudenone and fusaric acid may have some inhibjtory effects on epinephrine and norepinephrine biosynthesis in the mouse adrenal medulla. These results agree well with the biochemical data presented previously. Specific and potent inhibitors of the enzymes involved in catecholamine bio- synthesis have been recently discovered from the culture media of microorganisms by Umezawa et al (7, 11, 12, 13, 17). Oudenone ( (S)-2-[4, 5-dihydro- 5-propyl-2 (3H)-furylidene]-1, 3-cyclopentanedione) (12, 13, 17) is an inhibitor of tyrosine hydroxylase which was isolated from the culture filtrate of Oudenansiella radieata and shown to inhibit the enzyme in vivo to reduce the endogenous level of catecholamines. Fusaric acid (5-butylpicolinic acid) is an inhibtor of dopamine- ,3-hydroxylase which was isolated from the culture filtrate of a fungus of Fusarium species and shown to be a potent inhibitor of the enzyme in vitro and in vivo (7, 11).
    [Show full text]
  • Trichoderma: the “Secrets” of a Multitalented Biocontrol Agent
    plants Review Trichoderma: The “Secrets” of a Multitalented Biocontrol Agent 1, 1, 2 3 Monika Sood y, Dhriti Kapoor y, Vipul Kumar , Mohamed S. Sheteiwy , Muthusamy Ramakrishnan 4 , Marco Landi 5,6,* , Fabrizio Araniti 7 and Anket Sharma 4,* 1 School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH-1), Phagwara, Punjab 144411, India; [email protected] (M.S.); [email protected] (D.K.) 2 School of Agriculture, Lovely Professional University, Delhi-Jalandhar Highway, Phagwara, Punjab 144411, India; [email protected] 3 Department of Agronomy, Faculty of Agriculture, Mansoura University, Mansoura 35516, Egypt; [email protected] 4 State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou 311300, China; [email protected] 5 Department of Agriculture, University of Pisa, I-56124 Pisa, Italy 6 CIRSEC, Centre for Climatic Change Impact, University of Pisa, Via del Borghetto 80, I-56124 Pisa, Italy 7 Dipartimento AGRARIA, Università Mediterranea di Reggio Calabria, Località Feo di Vito, SNC I-89124 Reggio Calabria, Italy; [email protected] * Correspondence: [email protected] (M.L.); [email protected] (A.S.) Authors contributed equal. y Received: 25 May 2020; Accepted: 16 June 2020; Published: 18 June 2020 Abstract: The plant-Trichoderma-pathogen triangle is a complicated web of numerous processes. Trichoderma spp. are avirulent opportunistic plant symbionts. In addition to being successful plant symbiotic organisms, Trichoderma spp. also behave as a low cost, effective and ecofriendly biocontrol agent. They can set themselves up in various patho-systems, have minimal impact on the soil equilibrium and do not impair useful organisms that contribute to the control of pathogens.
    [Show full text]
  • Download Article (PDF)
    CHEMISTRY OF ENZYME INHffiiTORS OF MICROBIAL ORIGIN HAMAO UMEZAWA Institute of Microbial Chemistry and Department of Antibiotics, National Institute of Health, Tokyo, Japan ABSTRACT Study of antibiotics has furnished interesting materials to chemistry of natural products. I initiated the screening study of enzyme inhibitors produced by microorganisms and isolated Ieupeptin and antipain inhibiting trypsin and papain, chymostatin inhibiting chymotrypsin, pepstatin inhibiting pepsin, panosialin inhibiting sialidases, oudenone inhibiting tyrosine hydroxylase, dopastin inhibiting dopamine ß-hydroxylase, aquayamycin and chrothiomycin inhibiting tyrosine hydroxylase and dopamine ß-hydroxylase. Structures and syntheses ofmost ofthese compounds have been studied. I also found dopamine ß-hydroxylase-inhibiting activity of fusaric acid and oosponol, and xanthine­ oxidase inhibiting activity of 5-formyluracil which were produced by micro­ organisms. Chemical study of enzyme inhibitors has given useful information on the structurejactivity relation. The effect of pepstatin on stomach ulcer, and the hypotensive effect of oudenone and fusaric acid have been observed clinically. Enzyme inhibitors produced by microorganisms are the most valuable new area extended from antibiotics and will furnish new materials interesting in chemistry. biosynthesis, pharmacology, and utility. Research on antibiotics has contributed to the chemistry of natural products, furnishing materials of interesting structures, chemical syntheses, biosyntheses and of interesting
    [Show full text]
  • Isolation and Characterization of Two New Fusaric Acid Analogs from Fusarllun Lnonilijonne NRRL 13,163
    ApPLIED AND ENVIRONMENTAL MICROBIOLOGY. Aug. 1985. p. 311-314 Vol. 50. No.2 0099-2240/85/080311-04502.00/0 Copyright © 1985. American Society for Microbiology Isolation and Characterization of Two New Fusaric Acid Analogs from FusarlLun lnonilijonne NRRL 13,163 H. R. BURMEISTER." M. D. GROYE.t R. E. PETERSON. D. WEIS LEDER. AND R. D. PLATTNER Northern Regional Research Center, Agricultural Research Service. U.S. Department (~rAgricultllre, Peoria. Illinois 61604 Received 28 January 19851Accepted 14 May 1985 Fusarium monilijorme NRRL 13,163 produced two new fusaric acid analogs, a 10,11-dihydroxyfusaric acid and a diacid of fusaric acid in which the C-ll methyl was oxidized to a carboxyl. Several hundred milligrams of the 10,11-dihydroxyfusaric acid were routinely recovered from a kilogram of corn grit medium. It crystallized as white, irregularly shaped rectangles that melted at 153 to 154°C. The diacid analog of fusaric acid crystallized as white rods that melted at 210 to 211°C. Unlike the consistent recovery experienced with the 1O,11-dihydroxyfusaric acid, the diacid analog proved difficult to purify after the initial discovery and was detectable in subsequent fermentations only by mass spectrometry. Fusarium monilijorme Sheldon, a field fungus common on 3 days at ambient temperature followed by incubation for 18 many crops. including corn, small grains. millet. sorghum. days at 15°C. After incubation. 250 ml of methanol was and citrus fruits (1, 9), produces a number of interesting, added to each flask before the culture medium was macer­ biologically active secondary metabolites. The more studied ated in a Waring blender jar.
    [Show full text]
  • Induced Catecholamine Depletion in Patients with Seasonal Affective Disorder in Summer Remission Raymond W
    Effects of Alpha-Methyl-Para-Tyrosine- Induced Catecholamine Depletion in Patients with Seasonal Affective Disorder in Summer Remission Raymond W. Lam, M.D., Edwin M. Tam, M.D.C.M., Arvinder Grewal, B.A., and Lakshmi N. Yatham, M.B.B.S. Noradrenergic and dopaminergic mechanisms have been the control diphenhydramine session. The AMPT session proposed for the pathophysiology of seasonal affective resulted in higher depression ratings with all nine patients disorder (SAD). We investigated the effects of having significant clinical relapse, compared with two catecholamine depletion using ␣-methyl-para-tyrosine patients during the diphenhydramine session. All patients (AMPT), an inhibitor of tyrosine hydroxylase, in patients returned to baseline scores after drug discontinuation. with SAD in natural summer remission. Nine drug-free Catecholamine depletion results in significant clinical patients with SAD by DSM-IV criteria, in summer relapse in patients with SAD in the untreated, summer- remission for at least eight weeks, completed a double-blind, remitted state. AMPT-induced depressive relapse may be a crossover study. Behavioral ratings and serum HVA and trait marker for SAD, and/or brain catecholamines may MHPG levels were obtained for 3-day sessions during play a direct role in the pathogenesis of SAD. which patients took AMPT or an active control drug, [Neuropsychopharmacology 25:S97–S101, 2001] diphenhydramine.The active AMPT session significantly © 2001 American College of Neuropsychopharmacology. reduced serum levels of HVA and MHPG compared with Published by Elsevier Science Inc. KEY WORDS: Seasonal affective disorder; Alpha-methyl- pattern, with full remission of symptoms (or a switch para-tyrosine; Catecholamines; Dopamine; Noradrenaline; into hypomania/mania) during spring/summer.
    [Show full text]
  • X-Ray Fluorescence Analysis Method Röntgenfluoreszenz-Analyseverfahren Procédé D’Analyse Par Rayons X Fluorescents
    (19) & (11) EP 2 084 519 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 23/223 (2006.01) G01T 1/36 (2006.01) 01.08.2012 Bulletin 2012/31 C12Q 1/00 (2006.01) (21) Application number: 07874491.9 (86) International application number: PCT/US2007/021888 (22) Date of filing: 10.10.2007 (87) International publication number: WO 2008/127291 (23.10.2008 Gazette 2008/43) (54) X-RAY FLUORESCENCE ANALYSIS METHOD RÖNTGENFLUORESZENZ-ANALYSEVERFAHREN PROCÉDÉ D’ANALYSE PAR RAYONS X FLUORESCENTS (84) Designated Contracting States: • BURRELL, Anthony, K. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Los Alamos, NM 87544 (US) HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR (74) Representative: Albrecht, Thomas Kraus & Weisert (30) Priority: 10.10.2006 US 850594 P Patent- und Rechtsanwälte Thomas-Wimmer-Ring 15 (43) Date of publication of application: 80539 München (DE) 05.08.2009 Bulletin 2009/32 (56) References cited: (60) Divisional application: JP-A- 2001 289 802 US-A1- 2003 027 129 12164870.3 US-A1- 2003 027 129 US-A1- 2004 004 183 US-A1- 2004 017 884 US-A1- 2004 017 884 (73) Proprietors: US-A1- 2004 093 526 US-A1- 2004 235 059 • Los Alamos National Security, LLC US-A1- 2004 235 059 US-A1- 2005 011 818 Los Alamos, NM 87545 (US) US-A1- 2005 011 818 US-B1- 6 329 209 • Caldera Pharmaceuticals, INC. US-B2- 6 719 147 Los Alamos, NM 87544 (US) • GOLDIN E M ET AL: "Quantitation of antibody (72) Inventors: binding to cell surface antigens by X-ray • BIRNBAUM, Eva, R.
    [Show full text]
  • Fire Diamond HFRS Ratings
    Fire Diamond HFRS Ratings CHEMICAL H F R Special Hazards 1-aminobenzotriazole 0 1 0 1-butanol 2 3 0 1-heptanesulfonic acid sodium salt not hazardous 1-methylimidazole 3 2 1 corrosive, toxic 1-methyl-2pyrrolidinone, anhydrous 2 2 1 1-propanol 2 3 0 1-pyrrolidinecarbonyl chloride 3 1 0 1,1,1,3,3,3-Hexamethyldisilazane 98% 332corrosive 1,2-dibromo-3-chloropropane regulated carcinogen 1,2-dichloroethane 1 3 1 1,2-dimethoxyethane 1 3 0 peroxide former 1,2-propanediol 0 1 0 1,2,3-heptanetriol 2 0 0 1,2,4-trichlorobenzene 2 1 0 1,3-butadiene regulated carcinogen 1,4-diazabicyclo(2,2,2)octane 2 2 1 flammable 1,4-dioxane 2 3 1 carcinogen, may form explosive mixture in air 1,6-hexanediol 1 0 0 1,10-phenanthroline 2 1 0 2-acetylaminofluorene regulated carcinogen, skin absorbtion 2-aminobenzamide 1 1 1 2-aminoethanol 3 2 0 corrosive 2-Aminoethylisothiouronium bromide hydrobromide 2 0 0 2-aminopurine 1 0 0 2-amino-2-methyl-1,3-propanediol 0 1 1 2-chloroaniline (4,4-methylenebis) regulated carcinogen 2-deoxycytidine 1 0 1 2-dimethylaminoethanol 2-ethoxyethanol 2 2 0 reproductive hazard, skin absorption 2-hydroxyoctanoic acid 2 0 0 2-mercaptonethanol 3 2 1 2-Mercaptoethylamine 201 2-methoxyethanol 121may form peroxides 2-methoxyethyl ether 121may form peroxides 2-methylamino ethanol 320corrosive, poss.sensitizer 2-methyl-3-buten-2-ol 2 3 0 2-methylbutane 1 4 0 2-napthyl methyl ketone 111 2-nitrobenzoic acid 2 0 0 2-nitrofluorene 0 0 1 2-nitrophenol 2 1 1 2-propanol 1 3 0 2-thenoyltrifluoroacetone 1 1 1 2,2-oxydiethanol 1 1 0 2,2,2-tribromoethanol 2 0
    [Show full text]
  • A Computational Tool for Pathway-Based Rational Drug Repositioning Supplementary Information
    gene2drug: a Computational Tool for Pathway-based Rational Drug Repositioning Supplementary Information Francesco Napolitano1, Diego Carrella1, Barbara Mandriani1, Sandra Pisonero1, Diego Medina1, Nicola Brunetti-Pierri1,2, and Diego di Bernardo1,3 1Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), 80078, Italy. 2Department of Translational Medicine, Federico II University, 80131 Naples, Italy 3Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy. List of Figures S1 Relation between PPI network-based and pathway based approaches. Given a therapeutic gene and the set of pathways it is annotated to according to the different databases, the other genes in the same pathways are topologically closer to it in the PPI network as compared to randomly chosen genes. The average shortest path from the selected gene to other pathway members is reported on the y axis for each database. 3 S2 Size of intersection between existent evidence scores in the STITCH database (subset matched against the Cmap database) as a percentage of the total number of evidences. Numbers on the diagonal represent how many times a drug-target evidence exists divided by the total number of reported pairs. A \combined score" always exist if one of the other evidences exist, thus \combined score" covers 100% of the pairs. Conversely, an \experimental" score is only present for 14% of the pairs. The \Text mining" evidence strongly drives the \combined score" covering 61% of all the known protein-target interactions in STITCH. 4 S3 Relative luminescence units (RLU) in Hepa1-6 cells transfected with a plasmid ex- pressing the luciferase gene under the control of the GPT promoter and incubated with various concentrations of fulvestrant.
    [Show full text]
  • Characterization and Regulation of the Resistance-Nodulation-Cell
    Pletzer and Weingart BMC Microbiology 2014, 14:185 http://www.biomedcentral.com/1471-2180/14/185 RESEARCH ARTICLE Open Access Characterization and regulation of the Resistance-Nodulation-Cell Division-type multidrug efflux pumps MdtABC and MdtUVW from the fire blight pathogen Erwinia amylovora Daniel Pletzer and Helge Weingart* Abstract Background: The Gram-negative bacterium Erwinia amylovora is the causal agent of the devastating disease fire blight in rosaceous plants such as apple, pear, quince, raspberry, and cotoneaster. In order to survive and multiply in a host, microbes must be able to circumvent the toxic effects of antimicrobial plant compounds, such as flavonoids and tannins. E. amylovora uses multidrug efflux transporters that recognize and actively export toxic compounds out of the cells. Here, two heterotrimeric resistance-nodulation-cell division (RND)-type multidrug efflux pumps, MdtABC and MdtUVW, from E. amylovora were identified. These RND systems are unusual in that they contain two different RND proteins forming a functional pump. Results: To find the substrate specificities of the two efflux systems, we overexpressed the transporters in a hypersensitive mutant lacking the major RND pump AcrB. Both transporters mediated resistance to several flavonoids, fusidic acid and novobiocin. Additionally, MdtABC mediated resistance towards josamycin, bile salts and silver nitrate, and MdtUVW towards clotrimazole. The ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock was reduced. Quantitative RT-PCR analyses revealed that the expression of the transporter genes was induced during infection of apple rootstock. The polyphenolic plant compound tannin, as well as the heavy metal salt tungstate was found to induce the expression of mdtABC.
    [Show full text]
  • Prestwick Collection
    (-) -Levobunolol hydrochloride (-)-Adenosine 3',5'-cyclic monophosphate (-)-Cinchonidine (-)-Eseroline fumarate salt (-)-Isoproterenol hydrochloride (-)-MK 801 hydrogen maleate (-)-Quinpirole hydrochloride (+) -Levobunolol hydrochloride (+)-Isoproterenol (+)-bitartrate salt (+,-)-Octopamine hydrochloride (+,-)-Synephrine (±)-Nipecotic acid (1-[(4-Chlorophenyl)phenyl-methyl]-4-methylpiperazine) (cis-) Nanophine (d,l)-Tetrahydroberberine (R) -Naproxen sodium salt (R)-(+)-Atenolol (R)-Propranolol hydrochloride (S)-(-)-Atenolol (S)-(-)-Cycloserine (S)-propranolol hydrochloride 2-Aminobenzenesulfonamide 2-Chloropyrazine 3-Acetamidocoumarin 3-Acetylcoumarin 3-alpha-Hydroxy-5-beta-androstan-17-one 6-Furfurylaminopurine 6-Hydroxytropinone Acacetin Acebutolol hydrochloride Aceclofenac Acemetacin Acenocoumarol Acetaminophen Acetazolamide Acetohexamide Acetopromazine maleate salt Acetylsalicylsalicylic acid Aconitine Acyclovir Adamantamine fumarate Adenosine 5'-monophosphate monohydrate Adiphenine hydrochloride Adrenosterone Ajmalicine hydrochloride Ajmaline Albendazole Alclometasone dipropionate Alcuronium chloride Alexidine dihydrochloride Alfadolone acetate Alfaxalone Alfuzosin hydrochloride Allantoin alpha-Santonin Alprenolol hydrochloride Alprostadil Althiazide Altretamine Alverine citrate salt Ambroxol hydrochloride Amethopterin (R,S) Amidopyrine Amikacin hydrate Amiloride hydrochloride dihydrate Aminocaproic acid Aminohippuric acid Aminophylline Aminopurine, 6-benzyl Amiodarone hydrochloride Amiprilose hydrochloride Amitryptiline hydrochloride
    [Show full text]