DOCSLIB.ORG

Methods and Protocols M ETHODS in MOLECULAR BIOLOGY™

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Methods and Protocols M ETHODS in MOLECULAR BIOLOGY™ Methods in Molecular Biology 1055 Ute Roessner Daniel Anthony Dias Editors Metabolomics Tools for Natural Product Discovery Methods and Protocols M ETHODS IN MOLECULAR BIOLOGY™ Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hat fi eld, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 Metabolomics Tools for Natural Product Discovery Methods and Protocols Edited by Ute Roessner and Daniel Anthony Dias School of Botany, The University of Melbourne, Parkville, Victoria, Australia Editors Ute Roessner Daniel Anthony Dias School of Botany School of Botany The University of Melbourne The University of Melbourne Parkville, Victoria, Australia Parkville , Victoria , Australia ISSN 1064-3745 ISSN 1940-6029 (electronic) ISBN 978-1-62703-576-7 ISBN 978-1-62703-577-4 (eBook) DOI 10.1007/978-1-62703-577-4 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013945168 © Springer Science+Business Media, LLC 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. ©Photographed by Dr Britta Drevermann, Dandenong Ranges National Park, Tremont, Victoria, Australia (2012) Printed on acid-free paper Humana Press is a brand of Springer Springer is part of Springer Science+Business Media (www.springer.com) Pref ace The inspiration behind this volume of Methods in Molecular Biology: Metabolomics Tools for Natural Product Discoveries is to unite the diverse methodologies and protocols that have developed from classical natural product chemistry now transitioning to modern day metabolomics to identify bioactive secondary metabolites for the purpose of drug discov- ery. Natural product chemistry maybe regarded as an older science with the isolation of many natural products between the 1970s and 1990s mainly due to the advent of improved, highly sensitive separation methods, mass spectrometry, and nuclear magnetic resonance spectroscopy. Therefore, it is worthwhile to summarize recent advancements in current comprehensive analytical platforms and present how metabolomics is now being integrated into this classical fi eld to dereplicate and profi le natural product extracts. The aims of this book are to discuss and in part review, how natural product chemistry is transitioning to metabolomics as a result of the advent of comprehensive analytical plat- forms. Applications for the extraction of selected natural products (secondary metabolites) from less common sources such as bryophytes and hard corals are presented. Various bio- logical assays including anticancer, anti diabetic, antibacterial, and various metabolomic, biomarker, and dereplication strategies are discussed. Comprehensive applications and strategies for gas chromatography-mass spectrometry (GC-MS) (polar metabolite profi l- ing and fatty acid analysis), liquid chromatography-mass spectrometry (LC-MS) (untar- geted profi ling and lipidomics), and nuclear magnetic resonance (NMR) spectroscopy (profi ling) metabolomic-based studies are discussed. Finally, protocols and strategies for the structure elucidation of isolated natural products by NMR, determination of absolute confi gurations, and the discovery, biosynthesis, and engineering of novel enterocin and wailupemycin polyketide analogues and the synthesis of K 1 and K2 melatonin metabolites are presented. Methods in Molecular Biology: Metabolomics Tools for Natural Product Discoveries is tar- geted at chemists, biologists, pharmacologists, students, and researchers in related fi elds to appreciate the current available methodologies and protocols for natural product isolation, biomarker discovery, dereplication, biological assays, and comprehensive metabolomic plat- forms available for high-throughput analyses. Parkville , Victoria, Australia Ute Roessner Daniel Anthony Dias v Contents Preface . v Contributors . ix 1 Bryophytes: Liverworts, Mosses, and Hornworts: Extraction and Isolation Procedures . 1 Yoshinori Asakawa and Agnieszka Ludwiczuk 2 Plant Tissue Extraction for Metabolomics . 21 Ute Roessner and Daniel Anthony Dias 3 Detection of Polar Metabolites Through the Use of Gas Chromatography–Mass Spectrometry . 29 David P. De Souza 4 A Robust GC-MS Method for the Quantitation of Fatty Acids in Biological Systems. 39 Nirupama Samanmalie Jayasinghe and Daniel Anthony Dias 5 A Workflow from Untargeted LC-MS Profiling to Targeted Natural Product Isolation . 57 Damien L. Callahan and Candace E. Elliott 6 Lipidomics: Extraction Protocols for Biological Matrices . 71 Thusitha Wasntha Thilaka Rupasinghe 7 Metabolite Analysis of Biological Fluids and Tissues by Proton Nuclear Magnetic Resonance Spectroscopy . 81 John Robert Sheedy 8 NMR Spectroscopy: Structure Elucidation of Cycloelatanene A: A Natural Product Case Study. 99 Sylvia Urban and Daniel Anthony Dias 9 NMR-Based Metabolomics: A Probe to Utilize Biodiversity . 117 Lúcia P. Santos Pimenta, Hye Kyong Kim, Robert Verpoorte, and Young Hae Choi 10 Extraction Protocol for Nontargeted NMR and LC-MS Metabolomics-Based Analysis of Hard Coral and Their Algal Symbionts. 129 Benjamin R. Gordon, William Leggat, and Cherie A. Motti 11 Determination of Absolute Configuration Using Single Crystal X-Ray Diffraction . 149 Abigail L. Albright and Jonathan M. White 12 Natural Product Chemistry in Action: The Synthesis of Melatonin Metabolites K1 and K2 . 163 Helmut M. Hügel and Oliver A.H. Jones vii viii Contents 13 Discovery, Biosynthesis, and Rational Engineering of Novel Enterocin and Wailupemycin Polyketide Analogues . 171 John A. Kalaitzis 14 Bioassays for Anticancer Activities . 191 Janice McCauley, Ana Zivanovic, and Danielle Skropeta 15 Screening for Antidiabetic Activities . 207 Rima Caccetta and Hani Al Salami 16 Screening for Antibacterial, Antifungal, and Anti quorum Sensing Activity . 219 Elisa J. Hayhoe and Enzo A. Palombo 17 Metabolomics and Dereplication Strategies in Natural Products . 227 Ahmed Fares Tawfike, Christina Viegelmann, and RuAngelie Edrada-Ebel 18 Bridging the Gap: Basic Metabolomics Methods for Natural Product Chemistry . 245 Oliver A.H. Jones and Helmut M. Hügel 19 Strategies in Biomarker Discovery. Peak Annotation by MS and Targeted LC-MS Micro-Fractionation for De Novo Structure Identification by Micro-NMR . 267 Philippe J. Eugster, Gaëtan Glauser, and Jean-Luc Wolfender 20 Statistical Analysis of Metabolomics Data . 291 Alysha M.De Livera, Moshe Olshansky, and Terence P. Speed Index . 309 Contributors HANI AL SALAMI • Curtin Health Innovation Research Institute, School of Pharmacy, Curtin University , Perth , Australia ABIGAIL L. ALBRIGHT • School of Chemistry , The University of Melbourne , Melbourne , Australia ; Bio21 Institute (Molecular Science and Biotechnology Institute) , The University of Melbourne , Melbourne , Australia YOSHINORI ASAKAWA • Faculty of Pharmaceutical Sciences , Tokushima Bunri University , Tokushima , Japan RIMA CACCETTA • School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University , Perth , Australia DAMIEN L. CALLAHAN • Metabolomics Australia, School of Botany , The University of Melbourne , Parkville, VIC , Australia YOUNG HAE CHOI • Natural Products Laboratory, Institute of Biology, Leiden University , Leiden , The Netherlands ALYSHA M. DE LIVERA • Metabolomics Australia, Bio21 Institute (Molecular Science and Biotechnology Institute) , The University of Melbourne , Melbourne , Australia DAVID P. DE SOUZA • Metabolomics Australia, Bio21 Institute (Molecular Science and Biotechnology Institute) , The University of Melbourne , Melbourne , Australia DANIEL ANTHONY DIAS • School of Botany , The University of Melbourne , Parkville, Victoria , Australia RUANGELIE EDRADA-EBEL • Strathclyde Institute of Pharmacy and Biomedical Sciences , University of Strathclyde , Glasgow , UK CANDACE E. ELLIOTT • School of Botany , The University of Melbourne , Melbourne, Australia PHILIPPE J.
Load more

Recommended publications
  • Cell Line Descriptions Geneblazer® M1-NFAT
    Version No.: GeneBLAzer ® Validation Packet Page 1 of 5 01Sep08 Optimization of the GeneBLazer ® M1-NFAT-bla Jurkat Cell Line GeneBLAzer ® M1 NFAT-bla Jurkat Cells Catalog Numbers – K1710 Cell Line Descriptions GeneBLAzer ® M1-NFAT-bla Jurkat cells contain the human Acetylcholine (muscarinic) subtype 1 receptor (M1), (Accession # NM_000738 ) stably integrated into the CellSensor ® NFAT-bla Jurkat cell line. CellSensor ® NFAT-bla Jurkat cells (Cat. no. K1671) contain a beta-lactamase (bla ) reporter gene under control of the Nuclear Factor of Activated T-cells (NFAT) response element. M1-NFAT-bla Jurkat cells are functionally validated for Z’-factor and EC 50 concentrations of carbachol (Figure 1). In addition, GeneBLAzer ® M1-NFAT-bla CHO-K1 cells have been tested for assay performance under variable conditions. Target Description Muscarinic acetylcholine receptors are members of the G protein-coupled receptor (GPCR) superfamily. Muscarinic receptors are widely distributed and mediate the actions of acetylcholine in both the CNS and peripheral tissues. Five muscarinic receptor subtypes have been identified and are referred to as M 1-M5 (1-5). The five genes that encode the muscarinic receptors all belong to the rhodopsin-line family (Family A) and share strong sequence homology but have unique regions located at the amino terminus (extracellular) and in the third intracellular loop. The M 1, M3, and M 5 receptor subtypes couple through the G q/11 class of G-proteins and activate the phopholipase C pathway. Activation of this pathway in turn leads to increases in free intracellular calcium levels as inositol triphosphate mediates release of calcium from the endoplasmic reticulum.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110449 A1 Lorber Et Al
    US 200601 10449A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110449 A1 LOrber et al. (43) Pub. Date: May 25, 2006 (54) PHARMACEUTICAL COMPOSITION Publication Classification (76) Inventors: Richard R. Lorber, Scotch Plains, NJ (US); Heribert W. Staudinger, Union, (51) Int. Cl. NJ (US); Robert E. Ward, Summit, NJ A6II 3/473 (2006.01) (US) A6II 3L/24 (2006.01) Correspondence Address: A6IR 9/20 (2006.01) SCHERING-PLOUGH CORPORATION (52) U.S. Cl. ........................... 424/464; 514/290: 514/540 PATENT DEPARTMENT (K-6-1, 1990) 2000 GALLOPNG HILL ROAD KENILWORTH, NJ 07033-0530 (US) (57) ABSTRACT (21) Appl. No.: 11/257,348 (22) Filed: Oct. 24, 2005 The present invention relates to formulations useful for Related U.S. Application Data treating respiratory disorders associated with the production of mucus glycoprotein, skin disorders, and allergic conjunc (60) Provisional application No. 60/622,507, filed on Oct. tivitis while substantially reducing adverse effects associ 27, 2004. Provisional application No. 60/621,783, ated with the administration of non-selective anti-cholin filed on Oct. 25, 2004. ergic agents and methods of use thereof. US 2006/01 10449 A1 May 25, 2006 PHARMACEUTICAL COMPOSITION example, Weinstein and Weinstein (U.S. Pat. No. 6,086,914) describe methods of treating allergic rhinitis using an anti CROSS REFERENCE TO RELATED cholinergic agent with a limited capacity to pass across lipid APPLICATION membranes, such as the blood-brain barrier, in combination with an antihistamine that is limited in both sedating and 0001. This application claims benefit of priority to U.S.
    [Show full text]
  • In Vitro Pharmacology of Clinically Used Central Nervous System-Active Drugs As Inverse H1 Receptor Agonists
    0022-3565/07/3221-172–179$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 322, No. 1 Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics 118869/3215703 JPET 322:172–179, 2007 Printed in U.S.A. In Vitro Pharmacology of Clinically Used Central Nervous System-Active Drugs as Inverse H1 Receptor Agonists R. A. Bakker,1 M. W. Nicholas,2 T. T. Smith, E. S. Burstein, U. Hacksell, H. Timmerman, R. Leurs, M. R. Brann, and D. M. Weiner Department of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands (R.A.B., H.T., R.L.); ACADIA Pharmaceuticals Inc., San Diego, California (R.A.B., M.W.N., T.T.S., E.S.B., U.H., M.R.B., D.M.W.); and Departments of Pharmacology (M.R.B.), Neurosciences (D.M.W.), and Psychiatry (D.M.W.), University of California, San Diego, California Received January 2, 2007; accepted March 30, 2007 Downloaded from ABSTRACT The human histamine H1 receptor (H1R) is a prototypical G on this screen, we have reported on the identification of 8R- protein-coupled receptor and an important, well characterized lisuride as a potent stereospecific partial H1R agonist (Mol target for the development of antagonists to treat allergic con- Pharmacol 65:538–549, 2004). In contrast, herein we report on jpet.aspetjournals.org ditions. Many neuropsychiatric drugs are also known to po- a large number of varied clinical and chemical classes of drugs tently antagonize this receptor, underlying aspects of their side that are active in the central nervous system that display potent effect profiles.
    [Show full text]
  • TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
    US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage .
    [Show full text]
  • G Protein-Coupled Receptors
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading.
    [Show full text]
  • (Ph OH N N Me O YO O YO
    US 20070265293A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0265293 A1 Boyd et al. (43) Pub. Date: Nov. 15, 2007 (54) (S)-N-METHYLNALTREXONE Publication Classification (76) Inventors: Thomas A. Boyd, Grandview, NY (51) Int. Cl. (US); Howard Wagoner, Warwick, NY A6II 3L/4355 (2006.01) (US); Suketu P. Sanghvi, Kendall Park, A6M II/00 (2006.01) NJ (US); Christopher Verbicky, A6M I5/08 (2006.01) Broadalbin, NY (US); Stephen 39t. 35O C Andruski, Clifton Park, NY (US) (2006.01) A6IP 3L/00 (2006.01) Correspondence Address: St. 4. CR WOLF GREENFIELD & SACKS, P.C. (2006.01) 6OO ATLANTIC AVENUE 3G (i. 308: BOSTON, MA 02210-2206 (US) A6IP 33/02 (2006.01) C07D 489/00 (2006.01) (21) Appl. No.: 11/441,452 (52) U.S. Cl. .............. 514/282; 128/200.23; 128/202.17; (22) Filed: May 25, 2006 546/45 Related U.S. Application Data (57) ABSTRACT This invention relates to S-MNTX, methods of producing (60) Provisional application No. 60/684,570, filed on May S-MNTX, pharmaceutical preparations comprising 25, 2005. S-MNTX and methods for their use. O G M Br Br e (pH OH N N Me O YO O YO OH OH R-MNTX S-MNTX Patent Application Publication Nov. 15, 2007 Sheet 1 of 6 US 2007/0265293 A1 Fig. 1 OH OH Me-N Me-N D / O O -----BBr, O O CHCI NMP, 3 AUTOCLAVE, 70'C OMe OH 1 2 Br OH As GE) G As 69 GOH Me-N ION Me-N -lass O SO EXCHANGE O SO OH OH 3 S-MNTX 1 - OXYCODONE 2 - OXYMORPHONE 3 - ODIDE SALT OF S-MNTX Fig.
    [Show full text]
  • In Gtopdb V.2021.2
    IUPHAR/BPS Guide to Pharmacology CITE https://doi.org/10.2218/gtopdb/F2/2021.2 Acetylcholine receptors (muscarinic) in GtoPdb v.2021.2 Nigel J. M. Birdsall1, Sophie Bradley2, David A. Brown3, Noel J. Buckley4, R.A. John Challiss2, Arthur Christopoulos5, Richard M. Eglen6, Frederick Ehlert7, Christian C. Felder8, Rudolf Hammer9, Heinz J. Kilbinger10, Günter Lambrecht11, Chris Langmead5, Fred Mitchelson12, Ernst Mutschler11, Neil M. Nathanson13, Roy D. Schwarz14, David Thal5, Andrew B. Tobin2, Celine Valant5 and Jurgen Wess15 1. Francis Crick Institute, UK 2. University of Leicester, UK 3. University College London, UK 4. King's College London, UK 5. Monash University, Australia 6. PerkinElmer, UK 7. University of California Irvine, USA 8. Lilly Research Laboratories, USA 9. Nippon Boehringer Ingleheim, Japan 10. University of Mainz, Germany 11. University of Frankfurt, Germany 12. University of Melbourne, Australia 13. University of Washington, USA 14. Pfizer, USA 15. National Institutes of Health, USA Abstract Muscarinic acetylcholine receptors (mAChRs) (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [50]) are activated by the endogenous agonist acetylcholine. All five (M1-M5) mAChRs are ubiquitously expressed in the human body and are therefore attractive targets for many disorders. Functionally, M1, M3, and M5 mAChRs preferentially couple to Gq/11 proteins, whilst M2 and M4 mAChRs predominantly couple to Gi/o proteins. Both agonists and antagonists of mAChRs are clinically approved drugs, including pilocarpine for the treatment of elevated intra-ocular pressure and glaucoma, and atropine for the treatment of bradycardia and poisoning by muscarinic agents such as organophosphates. I Contents This is a citation summary for Acetylcholine receptors (muscarinic) in the Guide to Pharmacology database (GtoPdb).
    [Show full text]
  • United States Patent (10) Patent No.: US 8,003,794 B2 Boyd Et Al
    USO08003794B2 (12) United States Patent (10) Patent No.: US 8,003,794 B2 Boyd et al. (45) Date of Patent: Aug. 23, 2011 (54) (S)-N-METHYLNALTREXONE 4.385,078 A 5/1983 Onda et al. 4.427,676 A 1, 1984 White et al. (75) Inventors: Thomas A. Boyd, Grandview, NY (US); 4,430,327 A 2, 1984 Frederickson et al. 4,452,775 A 6, 1984 Kent Howard Wagoner, Warwick, NY (US); 4,457.907. A 7/1984 Porter et al. Suketu P. Sanghvi, Kendall Park, NJ 4.462,839 A 7/1984 McGinley et al. (US); Christopher Verbicky, 4,466,968 A 8, 1984 Bernstein Broadalbin, NY (US); Stephen t St. A s 3. Miley al. Andruski, Clifton Park, NY (US) 4,556,552- - - A 12/1985 Porter2 et al.a. 4,606,909 A 8/1986 Bechgaard et al. (73) Assignee: Progenics Pharmaceuticals, Inc., 4,615,885 A 10/1986 Nakagame et al. Tarrytown, NY (US) 4,670.287. A 6/1987 Tsuji et al. 4.675, 189 A 6, 1987 Kent et al. (*) Notice: Subject to any disclaimer, the term of this 4,689,332 A 8/1987 McLaughlin et al. patent is extended or adjusted under 35 2.7868 A SE Se U.S.C. 154(b) by 184 days. 4,765,978 A 8/1988 Abidi et al. 4,806,556 A 2/1989 Portoghese (21) Appl. No.: 12/460,507 4,824,853. A 4, 1989 Walls et al. 4,836,212 A 6, 1989 Schmitt et al. (22) Filed: Jul. 20, 2009 4,837.214 A 6, 1989 Tanaka et al.
    [Show full text]
  • Towards the Synthesis of Aromatic Analogues of Himbacine, Potential Muscarinic Ligands
    TOWARDS THE SYNTHESIS OF AROMATIC ANALOGUES OF HIMBACINE, POTENTIAL MUSCARINIC LIGANDS A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy by Xue Qin Shi (B.E., M.Sc.) Supervisor: Associate Professor Roger W. Read SCHOOL OF CHEMISTRY THE UNIVERSITY OF NEW SOUTH WALES MAY2000 CERTIFICATE OF ORIGNALITY I hereby declare thatthis submission is my own workand that, to the best of my knowledge and belief, it contains no material previously published or written by another person nor material which to a substantial extent has been accepted for the award of any other degree or diploma of a university or other institute of higher learning, except where due acknowledgementis made in thetext . CERTIFICATEOF ORIGINALITY I hereby declare that this submission is my own worlc and to the best of my knowledge it contains no materials previously published or written by another person, nor material which to a substantial extent bas been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. AJJ.y contnbution made to the research by others, with whom I have worlced at UNSW or elsewhere. is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged. 11 ACKNOLEDGEMENTS I am very grateful to my supervisor Associate Professor Roger W.
    [Show full text]
  • A Straightforward Route to Enantiopure Pyrrolizidines And
    Molecules 2001, 6, 142-193 molecules ISSN 1420-3049 http://www.mdpi.org Review Muscarinic Receptor Agonists and Antagonists Kenneth J. Broadley1 and David R. Kelly2,* 1Division of Pharmacology, Welsh School of Pharmacy and 2Department of Chemistry, Cardiff University, Cathays Park, Cardiff, CF10 3TB, UK *To whom correspondence should be addressed; e-mail: [email protected] Received: 2 August 2000; in revised form 16 January 2001 / Accepted: 16 January 2001 / Published: 28 February 2001 Abstract: A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes). Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted. Keywords: Alzheimer’s disease, nicotine, acetylcholine, arecoline, himbacine, tacrine, cyclostelletamines, intramolecular Diels-Alder reaction, indole alkaloids Contents 1 The Pharmacology of Muscarinic Receptors 1.1 Introduction 1.2 Muscarinic receptor subtypes Molecules 2001, 6 143 2 Pharmacological Effects of Agonists and Therapeutic Applications 2.1 Cardiovascular system 2.2 Gastointestinal tract 2.3 Other smooth muscle 2.4 Glandular secretions 2.5 The eye 2.6 Central nervous
    [Show full text]
  • V10a93-Yin Pgmkr
    Molecular Vision 2004; 10:787-93 <http://www.molvis.org/molvis/v10/a93> ©2004 Molecular Vision Received 22 December 2003 | Accepted 19 August 2004 | Published 13 October 2004 Muscarinic antagonist control of myopia: A molecular search for the M1 receptor in chick George C. Yin, Alex Gentle, Neville A. McBrien Department of Optometry and Vision Sciences, The University of Melbourne, Victoria, Australia Purpose: Pirenzepine, an M1 selective muscarinic antagonist, is effective in slowing the progression of myopia in both humans and experimental animals, including chick. As an M1 selective antagonist, pirenzepine is considered to mediate its effect through M1 receptors. However, there is currently no report of the M1 receptor in chicken. Therefore, if the mechanism of action of pirenzepine is similar across species, either the drug mediates its effect through a non-M1 mecha- nism, or M1 muscarinic receptors are present in chicken. The aim of the present study was to determine whether a genetic template for the M1 receptor was expressed, or even present, in chick. Methods: Polymerase Chain Reaction (PCR), and Southern and northern blotting analyses were used to search for M1 mRNA in chick ocular and brain tissues. PCR and Southern analyses were then used for searching the chick M1 gene and promoter. Appropriate rat positive controls were included throughout the study. Results: Direct mRNA detection by northern analysis showed no evidence of M1 mRNA expression in the chick ocular and brain tissues studied. Identical results were obtained from PCR amplification and were further confirmed by Southern analysis. Similarly, no M1 gene or promoter sequences were detected by PCR or Southern analyses.
    [Show full text]
  • Muscarinic Receptor Functioning and Distribution in The
    Muscarinic receptor GREGOR W. NIETGEN, JOERG SCHMIDT, LUTZ HESSE, CHRISTIAN W. HONEMANN, functioning and MARCEL E. DURIEUX distribution in the eye: molecular basis and implications for clinical diagnosis and therapy The role of neurotransmitters has generated number of receptors (cholinergic, adrenergic considerable interest over the last decade. and others) have been found in all types of Dale's first description in 1914 of the muscarinic ocular tissue: the functional consequence of and nicotinic components of the cholinergic their activation remains elusive but is currently systeml provided an explanation for the effects being investigated with great zeal. Glaucoma of various cholinergic active drugs on the eye. patients are still being treated with pilocarpine G.w. Nietgen J. Schmidt Parasympathetic cholinergic input to the human almost 40 years5 after its introduction to western L. Hesse iris sphincter muscle comes from neurons medicine in 1875.6 The development of specific Zentrum fOr whose axons make up the ciliary nerve, a muscarinic agonists (acetyl-j3-methylcholine) Augenheilkunde branch of the third cranial nerve. Acetylcholine and antagonists (scopolamine) followed. Philipps-Universitat Marburg is released by these neurons onto their target Cholinesterase was discovered in 19267 and Marburg, Germany 8 cells, the smooth muscle surrounding the pupil. named in 1932. At the same time carbachol was C.W. Honemann Muscarinic acetylcholine receptors on the synthesised,9 a drug resistant to cholinesterases M.E. Durieux surface of the muscle cells transduce the with a suitable specificity for glaucoma Departments of chemical signal into a muscle contraction which treatment.IO,ll Over the years various Pharmacology, Anaesthesiology and constricts the pupil.
    [Show full text]