DOCSLIB.ORG

Chemistry and Biology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemistry and Biology Peptides: Chemistry and Biology. Norbert Sewald, Hans-Dieter Jakubke Copyright © 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30405-3 (Hardback); 3-527-60068-X (Electronic) Norbert Sewald and Hans-Dieter Jakubke Peptides: Chemistry and Biology www.ShimiPedia.ir Peptides: Chemistry and Biology. Norbert Sewald, Hans-Dieter Jakubke Copyright © 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30405-3 (Hardback); 3-527-60068-X (Electronic) Norbert Sewald and Hans-Dieter Jakubke Peptides: Chemistry and Biology www.ShimiPedia.ir Peptides: Chemistry and Biology. Norbert Sewald, Hans-Dieter Jakubke Copyright © 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30405-3 (Hardback); 3-527-60068-X (Electronic) Prof. Dr. Norbert Sewald n This book was carefully produced. Nevertheless, Universität Bielefeld authors and publisher do not warrant the infor- Fakultät für Chemie mation contained therein to be free of errors. Organ. und Bioorgan. Chemie Readers are advised to keep in mind that state- PO Box 100131 ments, data, illustrations, procedural details or 33501 Bielefeld, Germany other items may inadvertently be inaccurate. Prof. em. Dr. Hans-Dieter Jakubke The use of general descriptive names, registered Universität Leipzig names, trademarks, etc. in this book does not im- Institut für Biochemie ply, even in the absence of a specific statement, Private address: that such names are exempt from the relevant Albert-Richter-Straße 12 protective laws and regulations and therefore free 01465 Dresden-Langebrück, Germany for general use. Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data Cover A catalogue record for this book is available from The cover picture shows the TPR1 domain of Hop the British Library. in complex with -Gly-Pro-Thr-Ile-Glu-Glu-Val- Die Deutsche Bibliothek – CIP-Cataloguing-in- Asp-OH (GPTIEEVD). TPR domains participate in Publication Data the ordered assembly of Hsp70-Hsp90 multichape- A catalogue record for this publication is available rone complexes. from Die Deutsche Bibliothek. The TPR1 domain of the adaptor protein Hop specifically recognizes the C-terminal heptapep- © WILEY-VCH Verlag GmbH tide -Pro-Thr-Ile-Glu-Glu-Val-Asp-OH (PTIEEVD) D-69469 Weinheim, 2002 of the chaperone Hsp70 while the TPR2A domain All rights reserved (including those of translation of Hop binds the C-terminal pentapeptide -Met- in other languages). No part of this book may be Glu-Glu-Val-Asp-OH (MEEVD) of the chaperone reproduced in any form – by photoprinting, mi- Hsp90. The EEVD motif is conserved in all solu- crofilm, or any other means – nor transmitted or ble forms of eukaryotic Hsp70 and Hsp90 pro- translated into machine language without written teins. permission from the publishers. Registered Peptide binding is mediated with the EEVD motif. names, trademarks, etc. used in this book, even Both carboxy groups of the C-terminal aspartate when not specifically marked as such, are not to anchor the peptide by electrostatic interactions. be considered unprotected by law. The hydrophobic residues located N-terminally Printed in the Federal Republic of Germany within the peptide are critical for specificity. Printed on acid-free paper [C. Scheufler, A. Brinker, G. Bourenkov, S. Pegora- Typesetting ro, L. Moroder, H. Bartunik, F.U. Hartl, I. Moarefi, K+V Fotosatz GmbH, Beerfelden Printing Structure of TPR domain-peptide complexes: criti- betz-druck gmbH, Darmstadt Bookbinding cal elements in the assembly of the Hsp70-Hsp90 J. Schäffer GmbH & Co.KG, multichaperone machine, Cell 2000, 101, 199; PDB Grünstadt entry 1ELW (http://www.rcsb.org/pdb/)] ISBN 3-527-30405-3 www.ShimiPedia.ir Peptides: Chemistry and Biology. Norbert Sewald, Hans-Dieter Jakubke V Copyright © 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30405-3 (Hardback); 3-527-60068-X (Electronic) Contents Preface XI Abbreviations XIII 1 Introduction and Background 1 2 Fundamental Chemical and Structural Principles 5 2.1 Definitions and Main Conformational Features of the Peptide Bond 5 2.2 Building Blocks, Classification, and Nomenclature 7 2.3 Analysis of the Covalent Structure of Peptides and Proteins 11 2.3.1 Separation and Purification 12 2.3.1.1 Separation Principles 12 2.3.1.2 Purification Techniques 16 2.3.1.3 Stability Problems 18 2.3.1.4 Evaluation of Homogeneity 19 2.3.2 Primary Structure Determination 20 2.3.2.1 End Group Analysis 21 2.3.2.2 Cleavage of Disulfide Bonds 23 2.3.2.3 Analysis of Amino Acid Composition 24 2.3.2.4 Selective Methods of Cleaving Peptide Bonds 25 2.3.2.5 N-Terminal Sequence Analysis (Edman Degradation) 27 2.3.2.6 C-terminal Sequence Analysis 29 2.3.2.7 Mass Spectrometry 30 2.3.2.8 Peptide Ladder Sequencing 32 2.3.2.9 Assignment of Disulfide Bonds and Peptide Fragment Ordering 33 2.3.2.10 Location of Post-Translational Modifications and Bound Cofactors 35 2.4 Three-Dimensional Structure 36 2.4.1 Secondary Structure 36 2.4.1.1 Helix 37 2.4.1.2 b-Sheet 38 2.4.1.3 Turns 39 2.4.1.4 Amphiphilic Structures 41 2.4.2 Tertiary Structure 43 2.4.2.1 Structure Prediction 46 www.ShimiPedia.ir VI Contents 2.5 Methods of Structural Analysis 47 2.5.1 Circular Dichroism 48 2.5.2 Infrared Spectroscopy 49 2.5.3 NMR Spectroscopy 50 2.5.4 X-Ray Crystallography 52 2.5.5 UV Fluorescence Spectroscopy 54 2.6 References 55 3 Biologically Active Peptides 61 3.1 Occurrence and Biological Roles 61 3.2 Biosynthesis 73 3.2.1 Ribosomal Synthesis 73 3.2.2 Post-translational Modification 76 3.2.2.1 Enzymatic Cleavage of Peptide Bonds 76 3.2.2.2 Hydroxylation 78 3.2.2.3 Carboxylation 78 3.2.2.4 Glycosylation 78 3.2.2.5 Amidation 83 3.2.2.6 Phosphorylation 83 3.2.2.7 Lipidation 85 3.2.2.8 Pyroglutamyl Formation 86 3.2.2.9 Sulfatation 87 3.2.3 Nonribosomal Synthesis 88 3.3 Selected Bioactive Peptide Families 90 3.3.1 Peptide and Protein Hormones 90 3.3.1.1 Liberins and Statins 92 3.3.1.2 Pituitary Hormones 96 3.3.1.3 Neurohypophyseal Hormones 98 3.3.1.4 Gastrointestinal Hormones 99 3.3.1.5 Pancreatic Islet Hormones 100 3.3.1.6 Further Physiologically Relevant Peptide Hormones 103 3.3.2 Neuropeptides 107 3.3.2.1 Opioid Peptides 109 3.3.2.2 Tachykinins 114 3.3.2.3 Further Selected Neuroactive Peptides 116 3.3.3 Peptide Antibiotics 119 3.3.3.1 Nonribosomally Synthesized Peptide Antibiotics 119 3.3.3.2 Ribosomally Synthesized Peptide Antibiotics 124 3.3.4 Peptide Toxins 126 3.4 References 130 4 Peptide Synthesis 135 4.1 Principles and Objectives 135 4.1.1 Main Targets of Peptide Synthesis 135 4.1.1.1 Confirmation of Suggested Primary Structures 135 www.ShimiPedia.ir Contents VII 4.1.1.2 Design of Bioactive Peptide Drugs 136 4.1.1.3 Preparation of Pharmacologically Active Peptides and Proteins 137 4.1.1.4 Synthesis of Model Peptides 138 4.1.2 Basic Principles of Peptide Bond Formation 139 4.2 Protection of Functional Groups 142 a 4.2.1 N -Amino Protection 143 4.2.1.1 Alkoxycarbonyl-Type (Urethane-Type) Protecting Groups 143 4.2.1.2 Carboxamide-Type Protecting Groups 152 4.2.1.3 Sulfonamide and Sulfenamide-Type Protecting Groups 152 4.2.1.4 Alkyl-Type Protecting Groups 153 a 4.2.2 C -Carboxy Protection 154 4.2.2.1 Esters 155 4.2.2.2 Amides and Hydrazides 157 a 4.2.3 C-terminal and Backbone N -Carboxamide Protection 160 4.2.4 Side-chain Protection 162 4.2.4.1 Guanidino Protection 162 4.2.4.2 x-Amino Protection 165 4.2.4.3 x-Carboxy Protection 166 4.2.4.4 Thiol Protection 168 4.2.4.5 Imidazole Protection 171 4.2.4.6 Hydroxy Protection 174 4.2.4.7 Thioether Protection 176 4.2.4.8 Indole Protection 177 4.2.4.9 x-Amide Protection 178 4.2.5 Enzyme-labile Protecting Groups 180 a 4.2.5.1 Enzyme-labile N -Amino Protection 181 a 4.2.5.2 Enzyme-labile C -Carboxy Protection and Enzyme-labile Linker Moieties 182 4.2.6 Protecting Group Compatibility 184 4.3 Peptide Bond Formation 184 4.3.1 Acyl Azides 185 4.3.2 Anhydrides 186 4.3.2.1 Mixed Anhydrides 187 4.3.2.2 Symmetrical Anhydrides 189 4.3.2.3 N-Carboxy Anhydrides 190 4.3.3 Carbodiimides 191 4.3.4 Active Esters 195 4.3.5 Acyl Halides 200 4.3.6 Phosphonium Reagents 201 4.3.7 Uronium Reagents 202 4.3.8 Further Special Methods 204 4.4 Racemization During Synthesis 205 4.4.1 Direct Enolization 205 4.4.2 5(4H)-Oxazolone Mechanism 205 4.4.3 Racemization Tests: Stereochemical Product Analysis 208 www.ShimiPedia.ir VIII Contents 4.5 Solid-Phase Peptide Synthesis (SPPS) 209 4.5.1 Solid Supports and Linker Systems 212 4.5.2 Safety-Catch Linkers 220 4.5.3 Protection Schemes 224 4.5.3.1 Boc/Bzl-protecting Groups Scheme (Merrifield Tactics) 224 4.5.3.2 Fmoc/tBu-protecting Groups Scheme (Sheppard Tactics) 225 4.5.3.3 Three- and More-Dimensional Orthogonality 227 4.5.4 Chain Elongation 227 4.5.4.1 Coupling Methods 227 4.5.4.2 Undesired Problems During Elongation 228 4.5.4.3 Difficult Sequences 230 4.5.4.4 On-Resin Monitoring 232 4.5.5 Automation of the Process 232 4.5.6 Special Methods 233 4.5.7 Peptide Cleavage from the Resin 235 4.5.7.1 Acidolytic Methods 235 4.5.7.2 Side reactions 236 4.5.7.3 Advantages and Disadvantages of the Boc/Bzl and Fmoc/tBu Schemes 237 4.5.8 Examples of Syntheses by Linear SPPS 237 4.6 Biochemical Synthesis 238 4.6.1 Recombinant DNA Techniques 239 4.6.1.1 Principles of DNA Technology 239 4.6.1.2 Examples of Synthesis by Genetic Engineering 243 4.6.1.3 Cell-free Translation Systems 244 4.6.2 Enzymatic Peptide Synthesis 247 4.6.2.1 Introduction 247 4.6.2.2 Approaches to Enzymatic Synthesis 248 4.6.2.3 Manipulations to Suppress Competitive Reactions 250 4.6.2.4 Irreversible C–N Ligations by Mimicking Enzyme Specificity 251 4.6.3 Antibody-catalyzed Peptide Bond Formation 253 4.7 References
Load more

Recommended publications
  • Evaluation of in Silico Approach for Prediction of Presence of Opioid Peptides in Wheat
    Evaluation of in silico approach for prediction of presence of opioid peptides in wheat This is the Accepted version of the following publication Garg, Swati, Apostolopoulos, Vasso, Nurgali, Kulmira and Mishra, Vijay Kumar (2018) Evaluation of in silico approach for prediction of presence of opioid peptides in wheat. Journal of Functional Foods, 41. 34 - 40. ISSN 1756-4646 The publisher’s official version can be found at https://www.sciencedirect.com/science/article/pii/S1756464617307454 Note that access to this version may require subscription. Downloaded from VU Research Repository https://vuir.vu.edu.au/36577/ 1 1 Evaluation of in silico approach for prediction of presence of opioid peptides in wheat 2 gluten 3 Abstract 4 Opioid like morphine and codeine are used for the management of pain, but are associated 5 with serious side-effects limiting their use. Wheat gluten proteins were assessed for the 6 presence of opioid peptides on the basis of tyrosine and proline within their sequence. Eleven 7 peptides were identified and occurrence of predicted sequences or their structural motifs were 8 analysed using BIOPEP database and ranked using PeptideRanker. Based on higher peptide 9 ranking, three sequences YPG, YYPG and YIPP were selected for determination of opioid 10 activity by cAMP assay against µ and κ opioid receptors. Three peptides inhibited the 11 production of cAMP to varied degree with EC50 values of YPG, YYPG and YIPP were 5.3 12 mM, 1.5 mM and 2.9 mM for µ-opioid receptor, and 1.9 mM, 1.2 mM and 3.2 mM for κ- 13 opioid receptor, respectively.
    [Show full text]
  • Lehman Caves Management Plan
    National Park Service U.S. Department of the Interior Great Basin National Park Lehman Caves Management Plan June 2019 ON THE COVER Photograph of visitors on tour of Lehman Caves NPS Photo ON THIS PAGE Photograph of cave shields, Grand Palace, Lehman Caves NPS Photo Shields in the Grand Palace, Lehman Caves. Lehman Caves Management Plan Great Basin National Park Baker, Nevada June 2019 Approved by: James Woolsey, Superintendent Date Executive Summary The Lehman Caves Management Plan (LCMP) guides management for Lehman Caves, located within Great Basin National Park (GRBA). The primary goal of the Lehman Caves Management Plan is to manage the cave in a manner that will preserve and protect cave resources and processes while allowing for respectful recreation and scientific use. More specifically, the intent of this plan is to manage Lehman Caves to maintain its geological, scenic, educational, cultural, biological, hydrological, paleontological, and recreational resources in accordance with applicable laws, regulations, and current guidelines such as the Federal Cave Resource Protection Act and National Park Service Management Policies. Section 1.0 provides an introduction and background to the park and pertinent laws and regulations. Section 2.0 goes into detail of the natural and cultural history of Lehman Caves. This history includes how infrastructure was built up in the cave to allow visitors to enter and tour, as well as visitation numbers from the 1920s to present. Section 3.0 states the management direction and objectives for Lehman Caves. Section 4.0 covers how the Management Plan will meet each of the objectives in Section 3.0.
    [Show full text]
  • Proceedings of the United States National Museum
    Proceedings of the United States National Museum SMITHSONIAN INSTITUTION • WASHINGTON, D.C. Volume 111 1960 Number 3429 A REVISION OF THE GENUS OGCODES LATREILLE WITH PARTICULAR REFERENCE TO SPECIES OF THE WESTERN HEMISPHERE By Evert I. Schlinger^ Introduction The cosmopolitan Ogcodes is the largest genus of the acrocerid or spider-parasite family. As the most highly evolved member of the subfamily Acrocerinae, I place it in the same general line of develop- ment as Holops Philippi, Villalus Cole, Thersitomyia Hunter, and a new South African genus.^ Ogcodes is most closely associated with the latter two genera . The Ogcodes species have never been treated from a world point of view, and this probably accounts for the considerable confusion that exists in the literature. However, several large regional works have been published that were found useful: Cole (1919, Nearctic), Brunetti (192G, miscellaneous species of the world, mostly from Africa and Australia), Pleske (1930, Palaearctic), Sack (1936. Palaearctic), and Sabrosky (1944, 1948, Nearctic). Up to this time 97 specific names have been applied to species and subspecies of this genus. Of these, 19 were considered synonyms, hence 78 species were assumed valid. With the description of 14 new species and the addition of one new name while finding onl}^ five new synonyms, 1 Department of Biological Control, University of California, Riverside, Calif. • This new genus, along with other new species and genera, is being described in forthcoming papers by the author. 227 228 PROCEEDINGS OF THE NATIONAL MUSEUM vol. m we find there are now 88 world species and subspecies. Thus, the total number of known forms is increased by 16 percent.
    [Show full text]
  • Ligand-Gated Chloride Channels Are Receptors for Biogenic Amines in C
    Ligand-Gated Chloride Channels Are Receptors for Biogenic Amines in C. elegans The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Ringstad, N., N. Abe, and H. R. Horvitz. “Ligand-Gated Chloride Channels Are Receptors for Biogenic Amines in C. elegans.” Science 325, no. 5936 (July 2, 2009): 96-100. As Published http://dx.doi.org/10.1126/science.1169243 Publisher American Association for the Advancement of Science (AAAS) Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/84506 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike 3.0 Detailed Terms http://creativecommons.org/licenses/by-nc-sa/3.0/ NIH Public Access Author Manuscript Science. Author manuscript; available in PMC 2010 October 25. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Science. 2009 July 3; 325(5936): 96±100. doi:10.1126/science.1169243. Ligand-gated chloride channels are receptors for biogenic amines in C. elegans Niels Ringstad1,2, Namiko Abe1,2,3, and H. Robert Horvitz1 1HHMI, Department of Biology and McGovern Institute for Brain Research, MIT, Cambridge MA 02139 Abstract Biogenic amines such as serotonin and dopamine are intercellular signaling molecules that function widely as neurotransmitters and neuromodulators. We have identified in the nematode Caenorhabditis elegans three ligand-gated chloride channels that are receptors for biogenic amines: LGC-53 is a high-affinity dopamine receptor, LGC-55 is a high-affinity tyramine receptor, and LGC-40 is a low-affinity serotonin receptor that is also gated by choline and acetylcholine.
    [Show full text]
  • 2019-2020 Award Recipients
    2019-2020 AWARD RECIPIENTS The Office of Undergraduate Research and Creative Activities is pleased to announce the MAYS and RPG recipients for the 2019-2020 academic year. Please join us in congratulating these students and their faculty mentors. Major Academic Year Support (MAYS) Student: Kelly Ackerly Mentor: Dr. Daniel Greenberg Major: Psychology Department: Psychology An Exploration of Maternal Factors Affecting Children’s Autobiographical Memory In day-to-day interactions, mothers and their young children discuss memories of events they have experienced. Research has demonstrated the relationship between these interactions and the development of children’s memories. It is through these interactions that children learn how to interpret personal experiences and develop the skill of talking about them with others in a coherent way. Additionally, studies have found that children are more likely to form false memories—that is, inaccurate “memories” of events that did not actually occur – because their memories are more easily manipulated. In this study, we will explore whether the way mothers talk to their children about ambiguous events affects the children’s interpretations and memories of the event. We will also attempt to determine if there is a relationship between mothers’ negativity during discussions and their child’s formation of false memories. To explore this idea, mothers and their children (aged 3 to 6 years) are given a handful of ambiguous situations to interpret separately. Children are given the opportunity to make slime with a research assistant while a second research assistant acts out ambiguous situations that could have a positive or negative interpretation. The children are evaluated on the way they interpret the situations and whether they form a negative false memory.
    [Show full text]
  • Characterisation and Partial Purification of a Novel Prohormone Processing Enzyme from Ovine Adrenal Medulla
    Volume 246, number 1,2, 44-48 FEB 06940 March 1989 Characterisation and partial purification of a novel prohormone processing enzyme from ovine adrenal medulla N. Tezapsidis and D.C. Parish Biochemistry Group, School of Biological Sciences, University of Sussex, Falmer, Brighton, Sussex, England Received 3 January 1989 An enzymatic activity has been identified which is capable of generating a product chromatographically identical with adrenorphin from the model substrate BAM 12P. This enzyme was purified by gel filtration and ion-exchange chromatog- raphy and characterised as having a molecular mass between 30 and 45 kDa and an acidic pL The enzyme is active at the acid pH expected in the secretory vesicle interior and is inhibited by EDTA, suggesting that it is a metalloprotease. This activity could not be mimicked by incubation with lysosomal fractions and it meets the criteria to be considered as a possible prohormone processing enzyme. Prohormone processing; Adrenorphin; Secretory vesiclepurification 1. INTRODUCTION The purification of an endopeptidase responsi- ble for the generation of adrenorphin was under- Active peptide hormones are released from their taken, using the ovine adrenal medulla as a source. precursors by endoproteolytic cleavage at highly Adrenorphin is known to be located in the adrenal specific sites. The commonest of these is cleavage medulla of all species so far investigated [6]. at pairs of basic residues such as lysine and Secretory vesicles (also known as chromaffin arginine [1,2]. However another common class of granules) were isolated as a preliminary purifica- processing sites are known to be at single arginine tion step, since it is known that prohormone pro- residues, adjacent to a proline [3].
    [Show full text]
  • 2009 Vermilion, Alberta
    September 2010 ISSN 0071‐0709 PROCEEDINGS OF THE 57th ANNUAL MEETING OF THE Entomological Society of Alberta November 5‐7, 2009 Vermilion, Alberta Content Entomological Society of Alberta Board of Directors for 2009 .............................................................. 3 Annual Meeting Committees for 2009 ................................................................................................. 3 President’s Address ............................................................................................................................. 4 Program of the 57th Annual Meeting.................................................................................................... 6 Oral Presentation Abstracts ................................................................................................................10 Poster Presentation Abstracts.............................................................................................................21 Index to Authors.................................................................................................................................24 Minutes of the Entomology Society of Alberta Executive/Board of Directors Meeting ........................26 Minutes of the Entomological Society of Alberta 57th Annual General Meeting...................................29 2009 Regional Director to the Entomological Society of Canada Report ..............................................32 2009 Northern Director’s Reports .......................................................................................................33
    [Show full text]
  • Meeting Key Synthetic Challenges in Amanitin Synthesis with a New Cytotoxic Analog: 50-Hydroxy- Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 50-hydroxy- Cite this: Chem. Sci., 2020, 11, 11927 0 † All publication charges for this article 6 -deoxy-amanitin have been paid for by the Royal Society of Chemistry Alla Pryyma, Kaveh Matinkhoo, Antonio A. W. L. Wong and David M. Perrin * Appreciating the need to access synthetic analogs of amanitin, here we report the synthesis of 50-hydroxy- Received 29th July 2020 60-deoxy-amanitin, a novel, rationally-designed bioactive analog and constitutional isomer of a-amanitin, Accepted 2nd October 2020 that is anticipated to be used as a payload for antibody drug conjugates. In completing this synthesis, we DOI: 10.1039/d0sc04150e meet the challenge of diastereoselective sulfoxidation by presenting two high-yielding and rsc.li/chemical-science diastereoselective sulfoxidation approaches to afford the more toxic (R)-sulfoxide. drug-tolerant cell subpopulations.7 Examples include ADCs for Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Introduction targeting human epidermal growth factor receptor 2 and pros- 8 9 a-Amanitin, the deadliest of the amatoxins produced by the tate specic membrane antigen. With but a few exceptions, death-cap mushroom Amanita phalloides, is a potent, orally nearly all bioconjugates to a cytotoxic amanitin have emerged 1 a available inhibitor of RNA polymerase II (pol II) (Ki 10 nM), from naturally-sourced -amanitin. To date, conjugation that has been validated as a payload for targeted cancer handles used for a-amanitin-based bioconjugates include the d- 2a therapy.2 First described in 1907 3 and isolated in 1941,4 a- hydroxyl of (2S,3R,4R)-4,5-dihydroxyisoleucine (DHIle), the 10 0 amanitin is a compact bicyclic octapeptide that has been asparagine side chain, and the 6 -hydroxyl of the tryptathio- 11 indispensable for probing RNA pol II-catalysed transcription in nine staple.
    [Show full text]
  • Genscript Product Catalog 2013-2014 Genscript Product Catalog
    GenScript Product Catalog 2013-2014 GenScript Product Catalog www.genscript.com GenScript USA Inc. 860 Centennial Ave. Piscataway, NJ 08854USA Tel: 1-732-885-9188 / 1-732-885-9688 Toll-Free Tel: 1-877-436-7274 Fax: 1-732-210-0262 / 1-732-885-5878 Email: [email protected] Nucleic Acid Purification and Analysis Business Development Tel: 1-732-317-5088 PCR PCR and Cloning Email: [email protected] Protein Analysis Antibodies 2013-2014 Peptides Welcome to GenScript GenScript USA Incorporation, founded in 2002, is a fast-growing biotechnology company and contract research organization (CRO) specialized in custom services and consumable products for academic and pharmaceutical research. Built on our assembly-line mode, one-stop solutions, continuous improvement, and stringent IP protection, GenScript provides a comprehensive portfolio of products and services at the most competitive prices in the industry to meet your research needs every day. Over the years, GenScript’s scientists have developed many innovative technologies that allow us to maintain our position at the cutting edge of biological and medical research while offering cost-effective solutions for customers to accelerate their research. Our advanced expertise includes proprietary technology for custom gene synthesis, OptimumGeneTM codon optimization technology, CloneEZ® seamless cloning technology, FlexPeptideTM technology for custom peptide synthesis, BacPowerTM technology for protein expression and purification, T-MaxTM adjuvant and advanced nanotechnology for custom antibody production, as well as our ONE-HOUR WesternTM detection system and eStain® protein staining system. GenScript offers a broad range of reagents, optimized kits, and system solutions to help you unravel the mysteries of biology. We also provide a comprehensive portfolio of customized services that include Bio-Reagent, Bio-Assay, Lead Optimization, and Antibody Drug Development which can be effectively integrated into your value chain and your operations.
    [Show full text]
  • Jump Takeoff in a Small Jumping Spider
    Journal of Comparative Physiology A https://doi.org/10.1007/s00359-021-01473-7 ORIGINAL PAPER Jump takeof in a small jumping spider Erin E. Brandt1,2 · Yoshan Sasiharan2 · Damian O. Elias1 · Natasha Mhatre2 Received: 27 October 2020 / Revised: 4 February 2021 / Accepted: 23 February 2021 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021 Abstract Jumping in animals presents an interesting locomotory strategy as it requires the generation of large forces and accurate timing. Jumping in arachnids is further complicated by their semi-hydraulic locomotion system. Among arachnids, jumping spiders (Family Salticidae) are agile and dexterous jumpers. However, less is known about jumping in small salticid species. Here we used Habronattus conjunctus, a small jumping spider (body length ~ 4.5 mm) to examine its jumping performance and compare it to that of other jumping spiders and insects. We also explored how legs are used during the takeof phase of jumps. Jumps were staged between two raised platforms. We analyzed jumping videos with DeepLabCut to track 21 points on the cephalothorax, abdomen, and legs. By analyzing leg liftof and extension patterns, we found evidence that H. conjunc- tus primarily uses the third legs to power jumps. We also found that H. conjunctus jumps achieve lower takeof speeds and accelerations than most other jumping arthropods, including other jumping spiders. Habronattus conjunctus takeof time was similar to other jumping arthropods of the same body mass. We discuss the mechanical benefts and drawbacks of a semi- hydraulic system of locomotion and consider how small spiders may extract dexterous jumps from this locomotor system.
    [Show full text]
  • Biological Redundancy of Endogenous GPCR Ligands in the Gut and the Potential for Endogenous Functional Selectivity
    REVIEW ARTICLE published: 28 November 2014 doi: 10.3389/fphar.2014.00262 Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity Georgina L. Thompson1, Meritxell Canals1 and Daniel P.Poole1,2 * 1 Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia 2 Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia Edited by: This review focuses on the existence and function of multiple endogenous agonists Dominique Massotte, Institut des of the somatostatin and opioid receptors with an emphasis on their expression in the Neurosciences Cellulaires et Intégratives, France gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular Reviewed by: Jakub Fichna, Medical University of or intracellular endopeptidases. In other examples, endogenous peptide agonists for the Lodz, Poland same G protein-coupled receptors can be products of distinct genes but contain high Pamela J. Hornby, Johnson & sequence homology. This apparent biological redundancy has recently been challenged Johnson, USA by the realization that different ligands may engender distinct receptor conformations *Correspondence: linked to different intracellular signaling profiles and, as such the existence of distinct Daniel P.Poole, Drug Discovery Biology, Monash Institute of ligands may underlie mechanisms to finely tune physiological responses. We propose that Pharmaceutical Sciences, 381 Royal further characterization of signaling pathways activated by these endogenous ligands will Parade, Parkville, VIC 3052, Australia provide invaluable insight into the mechanisms governing biased agonism. Moreover, these e-mail: [email protected] ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects.
    [Show full text]
  • Screening of 109 Neuropeptides on Asics Reveals No Direct Agonists
    www.nature.com/scientificreports OPEN Screening of 109 neuropeptides on ASICs reveals no direct agonists and dynorphin A, YFMRFamide and Received: 7 August 2018 Accepted: 14 November 2018 endomorphin-1 as modulators Published: xx xx xxxx Anna Vyvers, Axel Schmidt, Dominik Wiemuth & Stefan Gründer Acid-sensing ion channels (ASICs) belong to the DEG/ENaC gene family. While ASIC1a, ASIC1b and ASIC3 are activated by extracellular protons, ASIC4 and the closely related bile acid-sensitive ion channel (BASIC or ASIC5) are orphan receptors. Neuropeptides are important modulators of ASICs. Moreover, related DEG/ENaCs are directly activated by neuropeptides, rendering neuropeptides interesting ligands of ASICs. Here, we performed an unbiased screen of 109 short neuropeptides (<20 amino acids) on fve homomeric ASICs: ASIC1a, ASIC1b, ASIC3, ASIC4 and BASIC. This screen revealed no direct agonist of any ASIC but three modulators. First, dynorphin A as a modulator of ASIC1a, which increased currents of partially desensitized channels; second, YFMRFamide as a modulator of ASIC1b and ASIC3, which decreased currents of ASIC1b and slowed desensitization of ASIC1b and ASIC3; and, third, endomorphin-1 as a modulator of ASIC3, which also slowed desensitization. With the exception of YFMRFamide, which, however, is not a mammalian neuropeptide, we identifed no new modulator of ASICs. In summary, our screen confrmed some known peptide modulators of ASICs but identifed no new peptide ligands of ASICs, suggesting that most short peptides acting as ligands of ASICs are already known. Acid-sensing ion channels form a small family of proton-gated ion channels that belongs to the degenerin/epi- thelial Na+ channel (DEG/ENaC) gene family1.
    [Show full text]