The articles of the conference proceedings are published in Perspectives in Science (Volume 11, Pages 1-72, January 2017) and freely accessible.
Proceedings of the
4th Beilstein Glyco-Bioinformatics Symposium
Unravelling Glycan Complexity
22 – 26 June 2015, Potsdam, Germany
Unravelling glycan complexity – Prologue
Carsten Kettner and Martin G. Hicks
Beilstein-Institut, Frankfurt am Main, Germany
As a distinct discipline glycomics has gained significant impact over the past decade. The proteomics and genomics communities increasingly perceive glycans as essential elements in physiological and pathological processes rather than as decorative elements of lipids and proteins. Glycans are extremely complex and diverse in their structures and thus it has been necessary to develop a wide range of experimental techniques and instrumentation for their detection and analysis. With the advancement of techniques for the interactive and structural analysis of glycoconjugates their essential role in phenomena such as cell adherence, cell–cell interactions, molecular trafficking, biosynthetic quality control, signal transduction and host–pathogen recognition, became apparent...
The impact of defining glycan structures
Johannes F.G. Vliegenthart
Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 8435CH Utrecht, The Netherlands
For gaining insight in the mode of action at the molecular level of glycans in biological systems precise knowledge of the structure of the glycans is indispensable. To obtain this fundamental information well-defined starting material, optimal fractionation methods and adequate identification techniques are essential. In this review, the emphasis is on the application of high resolution 1H NMR spectroscopy to the structure determination of glycans of different origin. The power of 1H NMR spectroscopy is the possibility to determine in a non-destructive way all structural parameters of glycans. This is illustrated for glycans that differ in structural complexity...
Glycan arrays and other tools produced by automated glycan assembly
Peter H. Seeberger1,2
1Max-Planck Institute for Colloids and Interfaces, Am Mühlenberg 1, Potsdam 14476, Germany
2Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany
Carbohydrates are the dominant biopolymer on earth and play important roles ranging from building material for plants to function in many biological systems. Glycans remain poorly studied due to a lack of synthetic tools. The goal of my laboratory has been to develop a general method for the automated assembly of glycans. The general protocols we developed resulted in the commercialisation of the Glyconeer 2.1™ synthesizer as well as the building blocks and all reagents. Oligosaccharides as long as 50-mers are now accessible within days. Rapid access to defined oligosaccharides has been the foundation to many applications including synthetic tools such as glycan microarrays, glycan nanoparticles and anti-glycan antibodies. The platform technology is helping to address real-life problems by the creation of new vaccines and diagnostics. After addressing mainly mammalian glycobiology earlier, material science and plant biology are benefitting increasingly from synthetic glycans...
Latest developments in Semantic Web technologies applied to the glycosciences
Kiyoko F. Aoki-Kinoshita1,2, Nobuyuki P. Aoki1, Akihiro Fujita1, Noriaki Fujita2, Toshisuke Kawasaki3, Masaaki Matsubara4, Shujiro Okuda5, Toshihide Shikanai2, Daisuke Shinmachi1, Elena Solovieva2, Yoshinori Suzuki2, Shinichiro Tsuchiya1, Issaku Yamada4, Hisashi Narimatsu2
1Faculty of Science and Engineering, Soka University, Tokyo 192-8577, Japan
2Glycoscience and Glycotechnology Research Group, AIST, Ibaraki 305-8568, Japan
3Research Center for Glycobiotechnology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
4The Noguchi Institute, Tokyo 173-0003, Japan
5Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
The Integrated Life Science Database Project of Japan funded a group of glycoscientists to carry out a project to integrate glycoscience databases using Semantic Web technologies. As a continuation of the previous project period, the Japan Consortium for Glycobiology and Glycotechnology Database (JCGGDB) developed several glycoscience-related databases. The GlycoProtDB database is among those being integrated, providing an important resource to understand protein glycosylation. Another database being integrated is GlycoEpitope, a comprehensive database of carbohydrate epitopes and antibodies. In the current project period, we started the development of GlyTouCan, the international glycan structure repository providing unique accession numbers to all glycan structures. Although such databases are sufficiently important in and of themselves, their integration with other—omics data such as the protein information in UniProt will be crucial to bring glycosciences to the forefront of life sciences. However, to integrate such disparate sets of data among different fields in a way such that future maintenance costs are minimal, standardized ontologies and formats must be established. Our latest project has attempted to define the minimal standards that are necessary to enable this integration. The technical challenges to integrate all these databases and the technologies to overcome these challenges will be described...
GLYDE-II: The GLYcan data exchange format
Rene Ranzinger1, Krys J. Kochut2, John A. Miller2, Matthew Eavenson2, Thomas Lütteke3, William S. York1,2
1Complex Carbohydrate Research Center, University of Georgia, USA
2Computer Science Department, University of Georgia, USA
3Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen, Germany
The GLYcan Data Exchange (GLYDE) standard has been developed for the representation of the chemical structures of monosaccharides, glycans and glycoconjugates using a connection table formalism formatted in XML. This format allows structures, including those that do not exist in any database, to be unambiguously represented and shared by diverse computational tools. GLYDE implements a partonomy model based on human language along with rules that provide consistent structural representations, including a robust namespace for specifying monosaccharides. This approach facilitates the reuse of data processing software at the level of granularity that is most appropriate for extraction of the desired information. GLYDE-II has already been used as a key element of several glycoinformatics tools. The philosophical and technical underpinnings of GLYDE-II and recent implementation of its enhanced features are described...
Bioinformatics applications to aid high-throughput glycan profiling
Ian Walsh, Roisin O'Flaherty, Pauline M. Rudd
NIBRT GlycoScience Group, NIBRT—The National Institute for Bioprocessing, Research and Training, Foster's Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland
High-throughput methods to identify and quantify glycans in a given sample are rare. We have optimised a robotic platform for analysing biopharmaceuticals at each stage of the manufacturing process. In addition, it can be applied to basic research. The plate format makes it convenient for large sample sets; it is relatively cheap, robust and quantitative. However, the large datasets churned out by this platform require significant time to interpret. Consequently, informatics tool are required to help with this annotation. This article briefly describes our robotic platform and concentrates on a set of software tools for the interpretation of quantitative glycoprofiling data...
Bioinformatics of glycosaminoglycans
Han Hu1,2, Yang Mao2,3, Yu Huang2,3, Cheng Lin2,3, Joseph Zaia1,2,3
1Bioinformatics Program, Boston University, Boston, MA, USA
2Center for Biomedical Mass Spectrometry, Boston University, Boston, MA, USA
3Department of Biochemistry, Boston University, Boston, MA, USA
Cell surface heparan sulfates modulate many signalling pathways by binding growth factors and growth factor receptors. Expressed in a spatially and temporally regulated manner, these highly sulfated polysaccharides play important roles in all aspects of animal physiology. To understand heparan sulfate-protein binding, it is necessary to develop instrumental sequencing methods. Towards this end, we and others have demonstrated the effectiveness of activated electron dissociation (ExD) tandem mass spectrometry. The value in the ExD approach is that extremely rich tandem mass spectra are produced. The challenge is that bioinformatics methods are needed to convert the raw data into HS saccharide sequences. In this article we describe HS–SEQ, an algorithm developed for this purpose...
Complex carbohydrate recognition by proteins: Fundamental insights from bacteriophage cell adhesion systems
Nina K. Broeker1, Dorothee Andres1, Yu Kang2, Ulrich Gohlke3, Andreas Schmidt1, Sonja Kunstmann1, Mark Santer2, Stefanie Barbirz1
1Physikalische Biochemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Golm, Germany
2Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Golm, Germany
3Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, Robert-Rössle-Str. 10, 13125 Berlin, Germany
Protein–glycan interactions are ubiquitous in nature. Molecular description of complex formation and the underlying thermodynamics, however, are not well understood due to the lack of model systems. Bacteriophage tailspike proteins (TSP) possess binding sites for bacterial cell surfaces oligosaccharides. In this article we describe the analysis of TSP-oligosaccharide complexes. TSP provide large glycan interaction sites where affinity and specificity are guided by the protein surface solvation and the conformational space sampled by the respective glycan. Furthermore, we describe a computational approach to analyse the conformational space sampled by flexible glycans of bacterial origin, a prerequisite for a thorough understanding of TSP-oligosaccharide interactions...
2-C-Branched mannosides as a novel family of FimH antagonists – Synthesis and biological evaluation
Wojciech Schönemann, Marcel Lindegger, Said Rabbani, Pascal Zihlmann, Oliver Schwardt, Beat Ernst
Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland
Urinary tract infections (UTIs), which are among the most prevalent bacterial infections worldwide, are mainly attributed to uropathogenic Escherichia coli (UPEC). Because of frequent antibiotic treatment, antimicrobial resistance constitutes an increasing therapeutic problem. Antagonists of the mannose-specific bacterial lectin FimH, a key protein mediating the adhesion of UPEC to human bladder cells, would offer an alternative anti-adhesive treatment strategy. In general, FimH antagonists consist of a mannose moiety and a wide range of lipophilic aglycones. Modifications of the mannose core led to a distinct drop in affinity. A visual inspection of the crystal structure of FimH revealed a previously unexplored cavity surrounded by Ile13, Phe142 and Asp140, which could be reached by functional groups in the equatorial 2-position of the mannose. Here, we describe the synthesis of 2-C-branched mannosides and evaluation of their pharmacodynamic properties. ITC experiments with the selected antagonists revealed a drastic enthalpy loss for all 2-C-branched antagonists, which, however, is partially compensated by an entropy gain. This supports the hypothesis that the target cavity is too small to accommodate 2-C-substituents...
Protein–glycosaminoglycan interaction networks: Focus on heparan sulfate
Institute for Molecular and Supramolecular Chemistry and Biochemistry, UMR 5246 CNRS, University Lyon 1-INSA Lyon, CPE, Raulin Building, University Lyon 1, 43 Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France
Sulfated glycosaminoglycans (GAGs) are complex polysaccharides, which are covalently bound to protein cores to form proteoglycans. They are mostly located at the cell surface and in the extracellular matrix (ECM) where they regulate numerous biological processes. The aim of our work is (i) to identify and characterize protein–GAG interactions occurring at the cell surface and in the ECM, (ii) to study the assembly of multimolecular complexes formed at the cell surface via protein–heparan sulfate interactions, (iii) to determine the roles of these complexes in the ECM maturation and assembly, which are initiated in the pericellular matrix, and in pathological situations such as angiogenesis and host–pathogen interactions, (iv) to build, contextualize and analyze the corresponding protein–heparan sulfate interaction networks to identify molecular connections between the physio-pathological processes mentioned above and to select protein–GAG complexes specifically formed in a pathological situation and which might be therapeutic targets...
Epilogue—Unravelling Glycan Complexity
Weston B. Struwe
University of Oxford, Chemistry Department, Chemistry Research Laboratory, 12 Mansfield Road, Oxford Ox1 3TA, United Kingdom
The 4th Beilstein Glyco-Bioinformatics Symposium took place in Potsdam, Germany, and addressed several key issues facing the field of glycobiology. Presentations covered a range of disciplines from biology to computer science which provided a unique venue to discuss these challenges through an interdisciplinary approach. Researchers were offered an opportunity to not only present new research but also a unique environment to converse with other experts in the field and promote collaborations worldwide. The unique style of the Beilstein Symposia fosters a comfortable atmosphere which only furthers the exchange of ideas, knowledge and expertise to advance research in the glycosciences...