The Sugar Code E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 933

Veröffentlichungsjahr: 2011

Beschreibung

A reader friendly overview of the structure and functional relevance of natural glycosylation and its cognate proteins (lectins), this book is also one of the few books to cover their role in health and disease. Edited by one of the pioneering experts in the field and written by a team of renowned researchers this resource is a perfect introduction for all students in life and medical sciences, biochemistry, chemistry and pharmacy.
Website: WWW.WILEY-VCH.DE/HOME/THESUGARCODE

Leseprobe

Contents

Forewords

Preface

List of Contributors

PART ONE: CHEMICAL BASIS

1 THE BIOCHEMICAL BASIS AND CODING CAPACITY OF THE SUGAR CODEHAROLD RÜDIGER AND HANS-JOACHIM GABIUS

1.1 ETYMOLOGICAL ROOTS

1.2 WHAT PROJECTION FORMULAS TELL US

1.3 THE CODING CAPACITY OF THE SUGAR CODE

1.4 CONCLUSIONS

REFERENCES

2 THREE-DIMENSIONAL ASPECTS OF THE SUGAR CODETIBOR KOŽÁR, SABINE ANDRÉ, JOZEF ULINÝ, AND HANS-JOACHIM GABIUS

2.1 HOW TO OBTAIN INFORMATION ABOUT CARBOHYDRATE CONFORMATION

2.2 COMPLEXITY OF CARBOHYDRATE FLEXIBILITY

2.3 HOW TO DESCRIBE THE SHAPE OF MONOSACCHARIDES

2.4 HOW TO DESCRIBE THE SHAPE OF DI- AND OLIGOSACCHARIDES

2.5 ADDITIONAL FACTORS INFLUENCING THE SHAPE OF OLIGO- AND POLYSACCHARIDES

2.6 EXAMPLES OF DI- AND OLIGOSACCHARIDE CONFORMATIONS

2.7 CARBOHYDRATE–PROTEIN INTERMOLECULAR INTERACTIONS AND REACTION MECHANISMS

2.8 HOW TO PERFORM MOLECULAR MODELING OF LARGE GLYCANS

2.9 CONCLUSIONS

REFERENCES

3 THE CHEMIST’S WAY TO SYNTHESIZE GLYCOSIDESSTEFAN OSCARSON

3.1 SYNTHESIS OF OLIGOSACCHARIDES: STRATEGIES

3.2 GLYCOSIDIC BOND FORMATION

3.3 FISCHER GLYCOSYLATIONS

3.4 GLYCOSYL DONORS

3.5 ANOMERIC CONFIGURATION: STEREOSELECTIVITY

3.6 NEURAMINIC ACID AND KDO-GLYCOSIDE SYNTHESIS

3.7 FORMATION OF BUILDING BLOCKS: ORTHOGONAL GLYCOSYLATIONS

3.8 PROTECTING GROUP MANIPULATIONS

3.9 AN EXAMPLE

3.10 CONCLUSIONS

REFERENCES

4 THE CHEMIST’S WAY TO PREPARE MULTIVALENCYYOANN M. CHABRE AND RENÉ ROY

4.1 BLOCKING VIRAL/BACTERIAL ADHESION

4.2 HOW TO PREPARE MULTIVALENT CARBOHYDRATES?

4.3 NEOGLYCOPROTEINS

4.4 NEOGLYCOLIPIDS AND LIPOSOMES

4.5 GLYCOPOLYMERS

4.6 GLYCODENDRIMERS

4.7 GLYCODENDRIMER SYNTHESES

4.8 CONCLUSIONS

REFERENCES

5 ANALYTICAL ASPECTS: ANALYSIS OF PROTEIN-BOUND GLYCANSHIROAKI NAKAGAWA

5.1 DETECTION OF GLYCANS ON GLYCOPROTEINS

5.2 RELEASE OF GLYCANS FROM GLYCOPROTEINS

5.3 GLYCAN PURIFICATION

5.4 DETAILED STRUCTURAL ANALYSIS USING HPLC

5.5 DETAILED STRUCTURAL ANALYSIS USING MS

5.6 GLYCOMIC ANALYSIS USING MS

5.7 OTHER METHODS OF ANALYSIS

5.8 GLYCOPEPTIDE ANALYSIS USING MS

5.9 CONCLUSIONS

REFERENCES

PART TWO: NATURAL GLYCOSYLATION–GLYCOPROTEINS

6 N-GLYCOSYLATIONCHRISTIAN ZUBER AND JÜRGEN ROTH

6.1 NCAM1

6.2 INITIAL STEPS IN ASPARAGINE-LINKED GLYCOSYLATION

6.3 TRIMMING REACTIONS BY α-GLUCOSIDASES AND INTERACTIONS WITH ER LECTINS

6.4 QUALITY CONTROL OF PROTEIN FOLDING AND ASSEMBLY: MACHINERY AND PRINCIPAL MECHANISM

6.5 ER EXIT–FACING A CRUCIAL DECISION AND WHAT MANNOSE HAS TO DO

6.6 HOW TO BECOME A MATURE N-GLYCAN?

6.7 STRUCTURE BUILDING BY N-ACETYLGLUCOSAMINYLTRANSFERASE-I AND FUCOSYLTRANSFERASE-VIII

6.8 BRANCHING AND ELONGATION REACTIONS

6.9 DIVERSITY OF N-GLYCANS: STRUCTURAL AND FUNCTIONAL IMPLICATIONS

6.10 CONCLUSIONS

REFERENCES

7 O-GLYCOSYLATION: STRUCTURAL DIVERSITY AND FUNCTIONSGEORGIOS PATSOS AND ANTHONY CORFIELD

7.1 STRUCTURE OF O-LINKED GLYCANS

7.2 BIOSYNTHETIC ROUTES FOR O-GLYCANS

7.3 REGULATION OF O-GLYCOSYLATION AND GLYCAN PROCESSING

7.4 FUNCTIONS OF O-LINKED GLYCOSYLATION

7.5 MUCINS: A MAJOR GROUP OF O-GLYCOSYLATED PROTEINS

7.6 CONCLUSIONS

REFERENCES

8 GLYCOSYLATION OF MODEL AND ‘LOWER’ ORGANISMSIAIN B. H. WILSON, KATHARINA PASCHINGER, AND DUBRAVKO RENDI

8.1 BACTERIAL GLYCOSYLATION

8.2 YEAST GLYCOSYLATION

8.3 PLANT GLYCOSYLATION

8.4 INSECT GLYCOSYLATION

8.5 WORM GLYCOSYLATION

8.6 PROTOZOAN GLYCOSYLATION

8.7 FISH GLYCOSYLATION

8.8 CONCLUSIONS

REFERENCES

9 GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS: STRUCTURE, BIOSYNTHESIS AND FUNCTIONSHOSAM SHAMS-ELDIN, FRANÇOISE DEBIERRE-GROCKIEGO, AND RALPH T. SCHWARZ

9.1 STRUCTURE OF GPI ANCHORS

9.2 REMODELING OF LIPID MOIETIES OF GPI PROTEINS

9.3 CHEMICAL SYNTHESIS OF GPIS

9.4 CONCLUSIONS

REFERENCES

PART THREE: NATURAL GLYCOSYLATION–GLYCOLIPIDS, PROTEOGLYCANS AND CHITIN

10 GLYCOLIPIDSJÜRGEN KOPITZ

10.1 CLASSIFICATION AND GENERAL STRUCTURES OF GLYCOLIPIDS

10.2 GLYCOGLYCEROLIPIDS IN THYLAKOID MEMBRANES

10.3 GLYCOLIPIDS IN NON-PHOTOSYNTHETIC BACTERIA

10.4 BACTERIAL GLYCOLIPIDS IN T-CELL ACTIVATION

10.5 GLYCOSPHINGOLIPIDS (GSLS)

10.6 COMPLEX NEUTRAL GSLS

10.7 COMPLEX ACIDIC (ANIONIC) GSLS

10.8 SURVEY OF GSL FUNCTIONS

10.9 GSL MICRODOMAINS

10.10 GSLS AS ATTACHMENT SITES FOR VIRUSES, BACTERIA AND TOXINS

10.11 GSLS AS DEVELOPMENTAL OR DIFFERENTIATION MARKERS

10.12 TUMOR-ASSOCIATED GSL ANTIGENS

10.13 GANGLIOSIDES IN NEURAL TISSUE

10.14 GSL DEGRADATION AND GSL STORAGE DISORDERS

10.15 CONCLUSIONS

REFERENCES

11 PROTEOGLYCANSECKHART BUDDECKE

11.1 GLYCOSAMINOGLYCANS: COMPONENTS OF PROTEOGLYCANS (PGS)

11.2 PGS

11.3 LARGE AGGREGATING (HYALURONAN-BINDING) PGS

11.4 SMALL LEUCINE-RICH PGS

11.5 BASEMENT MEMBRANE PGS

11.6 CELL-SURFACE (TRANSMEMBRANE) PGS

11.7 CONCLUSIONS

REFERENCES

12 CHITINHANS MERZENDORFER

12.1 OCCURRENCE

12.2 STRUCTURE

12.3 FUNCTION

12.4 METABOLISM

12.5 CONCLUSIONS

REFERENCES

PART FOUR: PROTEIN–CARBOHYDRATE INTERACTIONS

13 PROTEIN–CARBOHYDRATE INTERACTIONS: BASIC CONCEPTS AND METHODS FOR ANALYSISDOLORES SOLÍS, ANTONIO ROMERO, MARGARITA MENÉNDEZ, AND JESÚS JIMÉNEZ-BARBERO

13.1 ATOMIC FEATURES OF PROTEIN–SUGAR INTERACTIONS

13.2 ROLE OF WATER IN PROTEIN–SUGAR INTERACTIONS

13.3 SELECTION OF CARBOHYDRATE CONFORMERS BY PROTEINS

13.4 THERMODYNAMICS OF PROTEIN–CARBOHYDRATE INTERACTIONS

13.5 CONCLUSIONS

REFERENCES

14 HOW TO DETERMINE SPECIFICITY: FROM LECTIN PROFILING TO GLYCAN MAPPING AND ARRAYSHIROAKI TATENO, ATSUSHI KUNO, AND JUN HIRABAYASHI

14.1 QUANTITATIVE ASPECTS OF LECTIN AFFINITY

14.2 FRONTAL AFFINITY CHROMATOGRAPHY (FAC) FOR SUGAR–PROTEIN INTERACTIONS

14.3 AUTOMATED FAC-FD SYSTEM

14.4 FROM ‘LECTIN PROFILING’ TO ‘GLYCAN MAPPING’

14.5 LECTIN MICROARRAY ENABLES MULTIPLEXED LECTIN–GLYCAN INTERACTION ANALYSIS

14.6 PRACTICE IN DIFFERENTIAL GLYCAN PROFILING: APPROACHES AND APPLICATIONS

14.7 CONCLUSIONS

REFERENCES

15 THE HISTORY OF LECTINOLOGYHAROLD RÜDIGER AND HANS-JOACHIM GABIUS

15.1 HOW LECTINOLOGY STARTED

15.2 EARLY DEFINITIONS

15.3 THE CURRENT DEFINITION OF THE TERM ‘LECTIN’

15.4 RECENT DEVELOPMENTS

15.5 CONCLUSIONS

REFERENCES

16 CA 2+: MASTERMIND AND ACTIVE PLAYER FOR LECTIN ACTIVITY (INCLUDING A GALLERY OF LECTIN FOLDS)HANS-JOACHIM GABIUS

16.1 CA 2+: ORGANIZING THE ACTIVE SITE

16.2 CA 2+: CONTACTING CHARGED LIGANDS 272

16.3 CA 2+: NEUTRALIZING NEGATIVE CHARGES AND CONTACTING NEUTRAL LIGANDS

16.4 CONCLUSIONS

REFERENCES

17 BACTERIAL AND VIRAL LECTINSJAN HOLGERSSON, ANKI GUSTAFSSON, AND STEFAN GAUNITZ

17.1 BACTERIAL LECTINS

17.2 VIRUS BINDING

17.3 CARBOHYDRATE-BASED ANTIINFECTIVES

17.4 CONCLUSIONS

REFERENCES

18 PLANT LECTINSHAROLD RÜDIGER AND HANS-JOACHIM GABIUS

18.1 NOMENCLATURE

18.2 FOLDING PATTERNS AND OCCURRENCE

18.3 PURIFICATION

18.4 APPLICATIONS

18.5 BIOLOGICAL FUNCTIONS

18.6 CONCLUSIONS

REFERENCES

19 ANIMAL AND HUMAN LECTINSHANS-JOACHIM GABIUS

19.1 PROTEIN FOLDS WITH LECTIN ACTIVITY

19.2 FUNCTIONS OF ANIMAL AND HUMAN LECTINS

19.3 LECTIN LIGANDS AND AFFINITY REGULATION

19.4 CONCLUSIONS

REFERENCES

20 ROUTES IN LECTIN EVOLUTION: CASE STUDY ON THE C-TYPE LECTIN-LIKE DOMAINSJILL E. GREADY AND ALEX N. ZELENSKY

20.1 C-TYPE LECTIN (CTL) EVOLUTION AS A CASE STUDY

20.2 CTL SUPERFAMILY: STRUCTURES AND GROUPS

20.3 MECHANISM OF CARBOHYDRATE BINDING

20.4 CTLS IN THE GENOME ERA

20.5 CTL DOMAIN-CONTAINING PROTEINS (CTLDCPS) IN METAZOANS FROM WHOLE-GENOME ANALYSIS

20.6 NON-METAZOAN CTLDS: FROM VIRUSES, BACTERIA AND PROTOZOA

20.7 CTLDCPS IN GENOMES OF PRE-METAZOANS AND PLANTS

20.8 CONCLUSIONS

REFERENCES

21 CARBOHYDRATE–CARBOHYDRATE INTERACTIONSIWONA BUCIOR, MAX M. BURGER, AND XAVIER FERNÀNDEZ-BUSQUETS

21.1 MOLECULAR BASIS OF CARBOHYDRATE–CARBOHYDRATE INTERACTIONS

21.2 CARBOHYDRATE–CARBOHYDRATE INTERACTIONS IN CELL RECOGNITION

21.3 CARBOHYDRATES AS DNA-BINDING MOTIFS

21.4 NEW STRATEGIES TO STUDY MULTIVALENT CARBOHYDRATE–CARBOHYDRATE INTERACTIONS

21.5 CONCLUSIONS

REFERENCES

PART FIVE: BIOMEDICAL ASPECTS AND CASE STUDIES

22 DISEASES OF GLYCOSYLATIONTHIERRY HENNET

22.1 N-GLYCOSYLATION

22.2 O-GLYCOSYLATION

22.3 GLYCOSAMINOGLYCANS

22.4 GLYCOSPHINGOLIPIDS

22.5 GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR

22.6 DEFECTS AFFECTING MULTIPLE CLASSES OF GLYCOSYLATION

22.7 TRAFFICKING DISORDERS

22.8 CONCLUSIONS

REFERENCES

23 ANIMAL MODELS TO DELINEATE GLYCAN FUNCTIONALITYKOICHI HONKE AND NAOYUKI TANIGUCHI

23.1 KNOCKOUT MOUSE

23.2 SPECIFIC FEATURES OF GLYCOGENE KO

23.3 OTHER GENE MANIPULATION TECHNIQUES

23.4 CONCLUSIONS

REFERENCES

24 GLYCOBIOLOGY OF FERTILIZATION AND EARLY EMBRYONIC DEVELOPMENTFELIX A. HABERMANN AND FRED SINOWATZ

24.1 PRIMER TO MAMMALIAN FERTILIZATION

24.2 THE FUNCTIONAL MORPHOLOGY OF THE ZONA PELLUCIDA (ZP)

24.3 THE GLYCOPROTEINS OF THE ZP AND THEIR ENCODING GENES

24.4 GLYCAN STRUCTURES OF ZP GLYCOPROTEINS

24.5 THE SYNTHESIS OF ZP GLYCOPROTEINS

24.6 LIGAND PROPERTIES OF ZP GLYCANS

24.7 THE GLYCOPROTEIN SHELL OF MAMMALIAN EMBRYOS

24.8 SURFACE GLYCANS OF STEM CELLS

24.9 CONCLUSIONS

REFERENCES

25 GLYCANS AS FUNCTIONAL MARKERS IN MALIGNANCY?SABINE ANDRÉ, JÜRGEN KOPITZ, HERBERT KALTNER, ANTONIO VILLALOBO, AND HANS-JOACHIM GABIUS

25.1 THE PAST

25.2 THE PRESENT

25.3 THE FUTURE

25.4 CONCLUSIONS

REFERENCES

26 SMALL IS BEAUTIFUL: MINI-LECTINS IN HOST DEFENSEROBERT I. LEHRER

26.1 MEET THE FAMILIES

26.2 WHERE DO α- AND β-DEFENSINS RESIDE?

26.3 INTRODUCING θ-DEFENSINS

26.4 INTRODUCING RETROCYCLINS

26.5 HEMAGGLUTINATION

26.6 HOW HIV-1 ENTERS TARGET CELLS

26.7 STUDIES WITH INFLUENZA A VIRUS

26.8 A TOXIC SIDE-TRIP

26.9 AND NOW, THE SURPRISE

26.10 IT TAKES TWO TO TANGLE

26.11 WHICH HUMAN α- AND θ-DEFENSINS ARE LECTINS?

26.12 CONCLUSIONS

REFERENCES

27 INFLAMMATION AND GLYCOSCIENCESREINHARD SCHWARTZ-ALBIEZ

27.1 SEQUENCE OF EVENTS

27.2 WHERE DO CARBOHYDRATE–LECTIN INTERACTIONS PLAY A ROLE DURING ACUTE INFLAMMATION?

27.3 SELECTINS

27.4 SELECTIN CARBOHYDRATE LIGANDS AND THEIR CARRIER GLYCOPROTEINS

27.5 GALECTINS

27.6 SIGLECS

27.7 OTHER LECTINS INVOLVED IN ANTIGEN RECOGNITION AND INFLAMMATORY PROCESSES

27.8 GLYCANS INVOLVED IN BACTERIA–HOST INTERACTIONS

27.9 GLYCOSYLATION IN INFLAMMATORY BOWEL DISEASES

27.10 CONCLUSIONS

REFERENCES

28 SUGARS AS PHARMACEUTICALSHELEN M. I. OSBORN AND ANDREA TURKSON

28.1 CANCER THERAPEUTICS

28.2 VIRAL INFECTIONS: HIV-1 AND INFLUENZA

28.3 DIABETES

28.4 CARBOHYDRATE-BASED ANTIBACTERIAL AGENTS

28.5 CARBOHYDRATE-BASED ANTITHROMBOTIC AGENTS

28.6 CONCLUSIONS

REFERENCES

29 PLATELET GLYCOPROTEINS AS LECTINS IN HEMATOLOGYKARIN HOFFMEISTER AND HERVÉ FALET

29.1 PLATELET PHYSIOLOGY

29.2 GPIB-IX–V COMPLEX

29.3 COLD-INDUCED PLATELET CLEARANCE

29.4 LONG-TERM PLATELET REFRIGERATION MAY REVEAL NEW INSIGHTS INTO PLATELET CLEARANCE

29.5 P-SELECTIN AND PSGL-1

29.6 CONCLUSIONS

REFERENCES

30 NEUROBIOLOGY MEETS GLYCOSCIENCESROBERT W. LEDEEN AND GUSHENG WU

30.1 GLUCOSE AND GLYCOGEN AS ENERGY SOURCES

30.2 GANGLIOSIDES AS PRIMARY GLYCANS OF THE NERVOUS SYSTEM

30.3 GANGLIOSIDE METABOLISM

30.4 GANGLIOSIDES OF THE PERIPHERAL NERVOUS SYSTEM

30.5 GANGLIOSIDE FUNCTIONAL ACTIVITIES

30.6 NEURAL GLYCOPROTEINS: OVERVIEW

30.7 NEURAL RECOGNITION GLYCOPROTEINS

30.8 GLYCOPROTEINS OF THE SYNAPSE

30.9 GLYCOPROTEINS OF MYELIN

30.10 PROTEOGLYCANS AND EXTRACELLULAR MATRIX OF THE NERVOUS SYSTEM

30.11 CONCLUSIONS

REFERENCES

Glossary

Index

Further Reading

Demchenko, A. V. (ed.)

Handbook of Chemical GlycosylationAdvances in Stereoselectivity and Therapeutic Relevance

524 pages in 1 volumes with 492 figures and 14 tables 2008 Hardcover ISBN: 978-3-527-31780-6

Wong, C.-H. (ed.)

Carbohydrate-based Drug Discovery

980 pages in 2 volumes with 296 figures and 42 tables 2003 Hardcover ISBN: 978-3-527-30632-9

Ernst, B., Hart, G. W., Sinaÿ, P. (eds.)

Carbohydrates in Chemistry and Biology

2578 pages in 4 volumes with 949 figures and 111 tables 2000 Hardcover ISBN: 978-3-527-29511-1

The Editor

Prof. Dr. Hans-Joachim Gabius Ludwig-Maximilians-University Munich Faculty of Veterinary Medicine Department of Veterinary Sciences Chair of Physiological Chemistry Veterinärstrasse 13 80539 München Germany

Cover Staining for α2,6-sialylated N-glycans of a bovine blastocyst (together with DNA and F-actin staining; please see Fig. 24.4 for details) and for α2,8-linked polysialic acid of a rat embryo (please see Fig. 6.1 and Chapter 30.7 for details) is exemplarily illustrated to document the importance of glycosylation and protein-carbohydrate recognition, shown in the center (please see Fig. 13.1 for details), from fertilization and different stages of embryogenesis to reach the adult and enter the new cycle for progeny.

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.d-nb.de.

© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form–by photoprinting, microfilm, or any other means–nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

ISBN: 978-3-527-32089-9

Foreword

The book of life is written with a molecular alphabet that is not limited to the four letters of the genetic code. This fact is being increasingly recognized not only by chemists but also by biologists and physicians, who have termed emerging fields ‘molecular biology, molecular genetics, molecular medicine, molecular cardiology, etc’. For glycosciences, this is also the ‘age of the molecule’. Modern views largely accept that the co-and post-translational glycosylation of proteins has a function in molecular recognition. Protein-carbohydrate and carbohydrate-carbohydrate interactions control salient aspects of intra-and intercellular communication and trafficking, and are at the basis of a variety of essential biological phenomena, such as clearance of glycoproteins from the circulatory system, adhesion of infectious agents to host cells, and cell adhesion in the immune system, malignancy and metastasis.

To encode this complex biomolecular recognition ability, Nature has at its disposal a very powerful information tool, the sugar code. The role of reading the sugar-encoded messages is mainly played by a class of carbohydrate-binding proteins called lectins, which, together with their synthetic analogues and the complementary glycomimetics, have attracted the attention of many scientists with a different cultural background and training, coming from organic, medicinal and pharmaceutical chemistry, biochemistry, biology, medicine and even material science.

The modern concepts of glycosciences are not covered in the currently available organic chemistry, biochemistry and medicine textbooks, the former dealing mainly with the synthetic and conformational properties of carbohydrates and the last two with the biosynthesis of polysaccharides such as glycogen and the role of sugars as biochemical fuel in energy metabolism. Therefore, the textbook The Sugar Code, edited by Hans-Joachim Gabius, arrives at the right time and is highly welcome. Thanks to the Editor’s efforts, the 30 chapters are consistently structured around the sugar code concept, convincingly attaining the aim of teaching fundamentals and revealing the molecular relations between apparently different phenomena. All the most important topics of the field of glycosciences are elegantly treated in an easily digestible manner, from the classic structure and analysis of carbohydrates to glycoproteins and glycolipids, up to the modern aspects of lectinology. Of particular relevance for the interdisciplinary nature of this textbook are the interesting chapters on multivalency, versatility of protein-carbohydrate and carbohydrate-carbohydrate interactions, mammalian mini-lectins, and emerging biomedical relevance of the sugar code as well as the valuable frequent cross-referencing between chapters. Tables and figures in all cases are didactically well-tailored for teaching purposes.

The textbook will play a major role in helping teachers to introduce undergraduate and graduate students in chemistry, biochemistry, biology, pharmacy, medicine and bio-and nanotechnology to this fascinating and rapidly expanding field. Moreover, other scientists in academia and industry, even those having a loose contact with glycosciences, will also benefit from this outstanding book. The view that glycans are more complex and difficult to study than proteins and nucleic acids is no longer true: The Sugar Code textbook teaches us they are sweet and easy.

Parma, July 2009    Rocco Ungaro

Foreword

There are three major classes of biological macromolecules, all of which encode information essential for the life of the organism. Nucleic acids and proteins are linear molecules in which the individual subunits (nucleotides and amino acids, respectively) are linked by identical phosphate and peptide bonds, respectively. Glycans are significantly more complex. The linkages between individual subunits (monosaccharides such as hexoses, hexosamines, pentoses, etc.) are not identical; the anomeric carbon atom can be linked either by an alpha or beta bond to one of several carbon atoms on the adjoining monosaccharide. The resulting macromolecule may be linear or branched and may be covalently attached to a protein or lipid. Glycans are therefore highly efficient vehicles for information storage–more value for the money.

The apparatus required for glycan assembly is unique. Whereas the biosynthesis of nucleic acids and proteins is carried out by relatively simple template mechanisms, glycans require a complicated non-template assembly line (very similar to an automobile assembly line) where many different workers and machines (membranous organelles and vesicles, enzymes, transporters, structural proteins) function in harmony to manufacture the final product from a complex collection of primary building materials.

Glycosciences have received far less attention than they deserve in undergraduate, graduate and post-graduate life sciences courses. This is primarily because of the complexity of glycan structures and the diverse functions that have been attributed to them. There has also been a relative lack of suitable textbooks. The editor and authors of this book have fully succeeded to present the many aspects of glycosciences including their roots in a clear and efficient manner ready to enter classrooms. It is also gratifying that ‘Info boxes’ are used in this book to cover interesting ‘side’ topics relevant to the general discussion. An extensive ‘Glossary’ allows rapid access to unfamiliar terms. Glycobiology is a huge field that affects every known biological organism: prokaryotes, protozoa, fungi, plants, invertebrates and vertebrates. Since it is impossible to deal with everything, the highly relevant and important topics are covered in this book, and an excellent compromise between total knowledge and teaching requirements has been achieved.

The original concept of the Central Dogma by Francis Crick ignored post-translational modifications (such as protein glycosylation) that greatly magnify the functions of a single protein encoded by a particular gene. The above brief discussion should be sufficient to convince the reader that glycans certainly play pivotal functional roles in biology. This book provides the detailed evidence to teach this lesson.

Toronto, July 2009    Harry Schachter

Preface

Why this book? Carbohydrates are much, much more than simple biochemical fuels or–as polymers–the molecular concrete to convey stability to plants or insects. As obvious sign for a wide physiological role, glycan chains are also frequently presented by proteins and lipids. Their significance ‘is to impart a discrete recognitional role’ on the carrier (P. J. Winterburn and C. F. Phelps, 1972), the essence of the concept of the sugar code. The alphabet of its components (letters) and the sophisticated transport and enzymatic machinery for oligosaccharide (code word) formation provide the basis for the generation of these enormously versatile biochemical signals. They are handy for all aspects of bioregulation, because sugars are second to no other class of biomolecules in the capacity of information coding using oligomers. As instrumental as this feature is for far-reaching functionality in vivo the unsurpassed structural complexity automatically turns the task of breaking the sugar code into a highly demanding interdisciplinary challenge. With chemistry, biology and medicine being involved, there is the need for a coherent guide to the fundamentals of glycosciences designed for students and experts with interest in interdisciplinary work. As L. Stryer so elegantly and timelessly wrote in 1974, a textbook should give readers command of concepts and language and prepare a fertile ground for future discoveries. These are the aims of this multi-authored introduction to glycosciences.

The book is formatted to allow it to serve as a source for self-study and teaching, eventually enabling the reader to embrace the breadth of glycosciences at a comprehensible and professional level. To do so, all chapters are deliberately adjusted to a common standard and style and presented in a logical order from structure to biology and medicine. Illustrations and tables are designed to be ready for direct use in classrooms for lectures or even complete courses. Written by renowned experts and enthusiastic teachers, the chapters–with their concise summary boxes and entertaining info boxes–can even be read separately, to allow students and colleagues to be selective. Frequent cross-referencing between chapters is intended to minimize the need to turn to specialized literature to lay solid foundations. Consequently, aided by editorial encouragement, it was possible to limit the number of references. Complaints in this regard should be sent to me at [e-mail]. Naturally, any advice, criticism or suggestions on what to improve in order to best achieve our aims, that is to provide proper guidance and effective material for teaching as well as to fascinate and to inspire, are very welcome. So we invite you to contact us!

What you now hold in your hands would not have been possible without the enthusiasm and expertise of all members of the team of authors, without the invaluable advice, encouragement and help given by colleagues, Jürgen Kopitz and Harold Rüdiger deserve to be mentioned for being special friends, coworkers, Ruth Ohl and Herbert Kaltner deserve to be mentioned for being preciously dedicated and profoundly professional, and especially my wife Sigrun Ortrud along the way from project plan to product–and without an essential factor in teamwork, which quickly made its presence felt: the team spirit! It is a great pleasure and privilege for me to say ‘Thank you’, also for your interest. In the name of each and everyone involved we hope that you, our readers, enjoy the book and consider it helpful for your contribution to breaking the sugar code!

Munich, July 2009    Hans-Joachim Gabius

List of Contributors

Sabine André Ludwig-Maximilians-University Munich Faculty of Veterinary Medicine Department of Veterinary Sciences Chair of Physiological Chemistry Veterinärstrasse 13 80539 München Germany

Iwona Bucior University of California San Francisco Department of Medicine 513 Parnassus Avenue San Francisco, CA 94143 USA

Eckhart Buddecke University of Muenster Institute of Physiological Chemistry and Pathobiochemistry and Leibniz-Institute of Arteriosclerosis Research Domagkstrasse 3 48149 Münster Germany

Max M. Burger Friedrich Miescher Institute for Biomedical Research Novartis Research Foundation Novartis International AG 4002 Basel Switzerland

Yoann M. Chabre University of Québec at Montréal Department of Chemistry P.O. Box 8888, succ. Centre-Ville Montréal (Québec) H3C 3P8 Canada

Anthony Corfield Bristol Royal Infirmary Division of Clinical Sciences South Bristol Mucin Research Group Marlborough Street Bristol BS2 8HW UK

Françoise Debierre-Grockiego Philipps-University Marburg Medical School Medical Center for Hygiene and Medical Microbiology Institute for Virology Laboratory of Parasitology Robert-Koch-Strasse 17 35043 Marburg Germany

Hervé Falet Harvard Medical School Brigham and Women’s Hospital Department of Medicine 75 Francis Street Boston, MA 02115 USA

Xavier Fernàndez-Busquets University of Barcelona Institute for Bioengineering of Catalonia Nanoscience and Nanotechnology Baldiri Reixac 10-12 08028 Barcelona Spain

Hans-Joachim Gabius Ludwig-Maximilians-University Munich Faculty of Veterinary Medicine Department of Veterinary Sciences Chair of Physiological Chemistry Veterinärstrasse 13 80539 München Germany

Stefan Gaunitz Karolinska Institute Karolinska University Hospital in Huddinge Division of Clinical Immunology 141 86 Stockholm Sweden

Jill E. Gready Australian National University John Curtin School of Medical Research College of Medicine, Biology and Environment Computational Proteomics and Therapy Design Group Genome Biology Program GPO Box 334 Canberra ACT 2601 Australia

Anki Gustafsson Recopharma AB Hälsovägen 7 141 57 Huddinge Sweden

Felix A. Habermann Ludwig-Maximilians-University Munich Faculty of Veterinary Medicine Department of Veterinary Sciences Chair of Veterinary Anatomy (Histology, Embryology) Veterinärstrasse 13 80539 München Germany

Thierry Hennet University of Zurich Institute of Physiology Winterthurerstrasse 190 8057 Zürich Switzerland

Jun Hirabayashi National Institute of Advanced Industrial Science and Technology Research Center for Medical Glycoscience Lectin Application and Analysis Team AIST Tsukuba Central 2 1-1-1, Umezono Tsukuba, Ibaraki 305-8568 Japan

Karin M. Hoffmeister Harvard Medical School Brigham and Women’s Hospital Department of Medicine 75 Francis Street Boston, MA 02115 USA

Jan Holgersson Karolinska Institute Karolinska University Hospital in Huddinge Division of Clinical Immunology 141 86 Stockholm Sweden

Koichi Honke Kochi University Medical School Department of Biochemistry Kochi System Glycobiology Center Kohasu, Oko-cho, Nankoku Kochi 783-8505 Japan

Jesús Jiménez-Barbero Consejo Superior de Investigaciones Científicas Centro de Investigaciones Biológicas Biología Físico-Química Ramiro de Maeztu 9 28040 Madrid Spain

Herbert Kaltner Ludwig-Maximilians-University Munich Faculty of Veterinary Medicine Department of Veterinary Sciences Chair of Physiological Chemistry Veterinärstrasse 13 80539 München Germany

Jürgen Kopitz Ruprecht-Karls-University Heidelberg Medical School Institute of Pathology Applied Tumor Biology Im Neuenheimer Feld 220 69120 Heidelberg Germany

Tibor Kožár Slovak Academy of Sciences Department of Biophysics Institute of Experimental Physics Watsonova 47 04001 Košice Slovak Republic

Atsushi Kuno National Institute of Advanced Industrial Science and Technology Research Center for Medical Glycoscience Lectin Application and Analysis Team AIST Tsukuba Central 2 1-1-1, Umezono Tsukuba, Ibaraki 305-8568 Japan

Robert W. Ledeen University of Medicine & Dentistry of New Jersey New Jersey Medical School Department of Neurology & Neurosciences 185 South Orange Avenue Newark, NJ 07103-2714 USA

Robert I. Lehrer University of California Los Angeles David Geffen School of Medicine Department of Medicine 10833 Le Conte Avenue Los Angeles, CA 90095 USA

Margarita Menéndez Consejo Superior de Investigaciones Científicas Instituto de Química Física Rocasolano Serrano 119 28006 Madrid Spain

Hans Merzendorfer University of Osnabrueck Department of Biology/Chemistry Division of Animal Physiology Barbarastrasse 11 49069 Osnabrück Germany

Hiroaki Nakagawa Hokkaido University Graduate School of Advanced Life Science and Frontier Research Center for Post-Genomic Science and Technology Sapporo 001-0021 Japan (current address: Hitachi High-Technologies Co. Naka Application Center Hitachinaka 312-0057 Japan)

Helen M. I. Osborn University of Reading School of Pharmacy Whiteknights Reading RG6 6AD UK

Stefan Oscarson University College Dublin UCD School of Chemistry and Chemical Biology Centre for Synthesis and Chemical Biology Belfield, Dublin 4 Ireland

Katharina Paschinger University of Natural Resources and Applied Life Sciences Department of Chemistry Muthgasse 18 1190 Wien Austria

Georgios Patsos Bristol Royal Infirmary Division of Clinical Sciences South Bristol Mucin Research Group Marlborough Street Bristol BS2 8HW UK

Dubravko Rendi University of Natural Resources and Applied Life Sciences Department of Chemistry Muthgasse 18 1190 Wien Austria

Antonio Romero Consejo Superior de Investigaciones Científicas Centro de Investigaciones Biológicas Departamento de Ciencia de Proteínas Ramiro de Maeztu 9 28040 Madrid Spain

Jürgen Roth University of Zurich Department of Pathology Division of Cell and Molecular Pathology Schmelzbergstrasse 12 8091 Zürich Switzerland (current adress: Yonsei University Graduate School Department of Biomedical Science WCU Program 262 Seongsanro, Seodaemun-gu Seoul 120-749 Korea)

René Roy University of Québec at Montréal Department of Chemistry P.O. Box 8888, succ. Centre-Ville Montréal (Québec) H3C 3P8 Canada

Harold Rüdiger Julius-Maximilians-University Wuerzburg Institute of Pharmacy and Food Chemistry Am Hubland 97074 Würzburg Germany

Reinhard Schwartz-Albiez German Cancer Research Center Department of Translational Immunology Im Neuenheimer Feld 580 69120 Heidelberg Germany

Ralph T. Schwarz Philipps-University Marburg Medical School Medical Center for Hygiene and Medical Microbiology Institute for Virology Laboratory of Parasitology Robert-Koch-Strasse 17 35043 Marburg Germany

Hosam Shams-Eldin Philipps-University Marburg Medical School Medical Center for Hygiene and Medical Microbiology Institute for Virology Laboratory of Parasitology Robert-Koch-Strasse 17 35043 Marburg Germany

Fred Sinowatz Ludwig-Maximilians-University Munich Faculty of Veterinary Medicine Department of Veterinary Sciences Chair of Veterinary Anatomy (Histology, Embryology) Veterinärstrasse 13 80539 München Germany

Dolores Solís Consejo Superior de Investigaciones Científicas Instituto de Química Física Rocasolano Serrano 119 28006 Madrid Spain

Hiroaki Tateno National Institute of Advanced Industrial Science and Technology Research Center for Medical Glycoscience Lectin Application and Analysis Team AIST Tsukuba Central 2 1-1-1, Umezono Tsukuba, Ibaraki 305-8568 Japan

Naoyuki Taniguchi Osaka University Institute of Scientific and Industrial Research Department of Disease Glycomics Mihogaoka 8-1, Ibaraki Osaka 567-0047 Japan

Andrea Turkson University of Reading School of Pharmacy Whiteknights Reading RG6 6AD UK

Jozef Uliný Pavol Jozef Šafárik University Faculty of Science Department of Biophysics Jesenná 5 04145 Košice Slovak Republic

Antonio Villalobo Consejo Superior de Investigaciones Científicas Instituto de Investigaciones Biomédicas Arturo Duperier 4 28029 Madrid Spain

Iain B. H. Wilson University of Natural Resources and Applied Life Sciences Department of Chemistry Muthgasse 18 1190 Wien Austria

Gusheng Wu University of Medicine & Dentistry of New Jersey New Jersey Medical School Department of Neurology & Neurosciences 185 South Orange Avenue Newark, NJ 07103-2714 USA

Alex N. Zelensky Erasmus Medical Center Department of Genetics Dr. Molewaterplein 50 3015 GE Rotterdam The Netherlands

Christian Zuber University of Zurich Department of Pathology Division of Cell and Molecular Pathology Schmelzbergstrasse 12 8091 Zürich Switzerland

PART ONE

CHEMICAL BASIS