Claus-Wilhelm von der Lieth

German Cancer Research Center, Heidelburg, Baden-Württemberg, Germany

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Publications (61)163.43 Total impact

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    ABSTRACT: The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb.
    Glycobiology 11/2010; 21(4):493-502. · 3.54 Impact Factor
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    René Ranzinger, Stephan Herget, Claus-Wilhelm von der Lieth, Martin Frank
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    ABSTRACT: GlycomeDB integrates the structural and taxonomic data of all major public carbohydrate databases, as well as carbohydrates contained in the Protein Data Bank, which renders the database currently the most comprehensive and unified resource for carbohydrate structures worldwide. GlycomeDB retains the links to the original databases and is updated at weekly intervals with the newest structures available from the source databases. The complete database can be downloaded freely or accessed through a Web-interface (www.glycome-db.org) that provides flexible and powerful search functionalities.
    Nucleic Acids Research 11/2010; 39(Database issue):D373-6. · 8.81 Impact Factor
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    Hiren J Joshi, Claus-Wilhelm von der Lieth, Nicolle H Packer, Marc R Wilkins
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    ABSTRACT: The GlycoViewer (http://www.systemsbiology.org.au/glycoviewer) is a web-based tool that can visualize, summarize and compare sets of glycan structures. Its input is a group of glycan structures; these can be entered as a list in IUPAC format or via a sugar structure builder. Its output is a detailed graphic, which summarizes all salient features of the glycans according to the shapes of the core structures, the nature and length of any chains, and the types of terminal epitopes. The tool can summarize up to hundreds of structures in a single figure. This allows unique, high-level views to be generated of glycans from one protein, from a cell, a tissue or a whole organism. Use of the tool is illustrated in the analysis of normal and disease-associated glycans from the human glycoproteome.
    Nucleic Acids Research 07/2010; 38(Web Server issue):W667-70. · 8.81 Impact Factor
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    Carbohydrate Research. 04/2010; 345(6):860.
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    Journal of the American Chemical Society 02/2010; · 10.68 Impact Factor
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    ABSTRACT: The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi: 10.1016/j.carres.2010.01.003. The duplicate article has therefore been withdrawn.
    Carbohydrate research 02/2010; · 2.03 Impact Factor
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    ABSTRACT: The cyclic peptides c-(LSETTl) and c-(RTLPFS) are of potential clinical interest--they stimulate neurite outgrowth in a way that is similar to the effects of the HNK-1 (human natural killer cell-1) antigenic carbohydrate chains, which are terminated by 3'-sulfated glucuronic acid attached to an N-acetyllactosamine unit. To investigate the structure-activity relationships of the ability of the cyclic peptides to mimic HNK-1 carbohydrates, conformational analysis and examination of hydrophobic and hydrophilic patterns were performed and compared with the characteristics of a synthetic HNK-1 trisaccharide derivative. Data obtained demonstrate that both the trisaccharide and the glycomimetic peptide c-(LSETTl) exhibit a similar relationship between their hydrophobic moieties and their negatively charged sites. However, the second cyclic glycomimetic peptide investigated here, c-(RTLPFS), has a positively charged group as a potential contact point due to its Arg residue. Therefore, we studied the amino acid composition of all known receptor structures in the Protein Data Bank that are in contact with uronic acid and/or sulfated glycans. Interactions of the HNK-1 trisaccharide, c-(LSETTl), and c-(RTLPFS) with a laminin fragment involved in HNK-1 carbohydrate binding (i.e., the 21mer peptide: KGVSSRSYVGCIKNLEISRST) were also analyzed. Because the structure of the HNK-1-binding laminin domain is not available in the Protein Data Bank, we used the HNK-1-binding 21mer peptide fragment of laminin for the construction of a model receptor that enabled us to compare the molecular interplay of the HNK-1 trisaccharide and the two cyclopeptides c-(LSETTl) and c-(RTLPFS) with a reliable receptor structure in considerable detail.
    Journal of the American Chemical Society 01/2010; 132(1):96-105. · 10.68 Impact Factor
  • Thomas Lütteke, Claus-Wilhelm von der Lieth
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    ABSTRACT: Various databases that provide information on glycoenzymes are available on the Internet. In addition to the common protein databases there are several resources that specialize in glycoenzymes or contain an individual subsection for this kind of enzyme. This chapter provides an overview of existing databases aside from CAZy, such as the GlycoGene DataBase, KEGG, the CFG databases, ExPASy ENZYME, and BRENDA, and lists the kind of data that can be found in the individual resources. The majority of the specialized databases contain information on glycosyltransferases involved in glycan biosynthesis, while data on carbohydrate degrading enzymes is less often found.
    Bioinformatics for Glycobiology and Glycomics: An Introduction, 11/2009: pages 119 - 123; , ISBN: 9780470029619
  • Thomas Lütteke, Claus-Wilhelm von der Lieth
    Bioinformatics for Glycobiology and Glycomics: An Introduction, 11/2009: pages 433 - 445; , ISBN: 9780470029619
  • Stephan Herget, René Ranzinger, Robin Thomson, Martin Frank, Claus-Wilhelm von der Lieth
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    ABSTRACT: Yes Yes
    Bioinformatics for Glycobiology and Glycomics: An Introduction, 11/2009: pages 21 - 47; , ISBN: 9780470029619
  • Claus-Wilhelm von der Lieth, Thomas Lütteke
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    ABSTRACT: Glycosylation is the most common and most complex co- and posttranslational modification of proteins. Glycan chains can alter the physico-chemical properties of glycoproteins, and N-glycans also play an important role in the protein folding process. Glycosylated proteins on cell surfaces are implicated in various cell-cell and cell-matrix interactions. This chapter gives an overview of the various glycosylation types, and the functions and biosynthesis of the carbohydrate chains. A statistical analysis of the amino acids in the neighborhood of occupied glycosylation sites reveals different patterns of frequently found amino acids around N-glycosylation and O-glycosylation sites.
    Bioinformatics for Glycobiology and Glycomics: An Introduction, 11/2009: pages 143 - 162; , ISBN: 9780470029619
  • René Ranzinger, Martin Frank, Claus-Wilhelm von der Lieth, Stephan Herget
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    ABSTRACT: Despite ongoing harmonization efforts, the major carbohydrate sequence databases following the first initiative in this field, CarbBank, are still isolated islands, with mechanisms for automatic structure exchange and comparison largely missing. This unfavorable situation has been overcome with a systematic data integration effort, resulting in the GlycomeDB, a meta-database for public carbohydrate sequences. It contains at present 35,056 unique structures in GlycoCT encoding, referencing more than 100,000 external records from 1845 different taxonomic sources. We have created a user-friendly, web-based graphical interface which allows taxonomic and structural data to be entered and searched for. The structural search possibilities include substructure search, similarity search, and maximum common substructure. A novel search refinement mechanism allows the assembly of complex queries. With GlycomeDB (www.glycome-db.org), it is now possible to use a single portal to access all digitally encoded, public structural data in glycomics and to perform complex queries with the help of a web-based user interface.
    Glycobiology 09/2009; 19(12):1563-7. · 3.54 Impact Factor
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    ABSTRACT: The affinity to sialic acid-containing oligosaccharides of the small-animal lectin SHL-I isolated from the venom of the Chinese bird-hunting spider Selenocosmia huwena is here described for the first time. By a strategic combination of NMR techniques, molecular modeling, and data mining tools it was possible to identify the crucial amino acid residues that are responsible for SHL-I's ability to bind sialic acid residues in a specific way. Furthermore, we are able to discuss the role of the functional groups of sialic acid when bound to SHL-I. Also the impact of Pro31 in its cis- or trans-form on SHL-I's ligand affinity is of special interest, since it answers the question if Trp32 is a crucial amino acid for stabilizing complexes between SHL-I and sialic acid. SHL-I can be considered as a proper model system that provides further insights into the binding mechanisms of small-animal lectins to sialic acid on a sub-molecular level.
    Carbohydrate research 07/2009; 344(12):1515-25. · 2.03 Impact Factor
  • Claus-Wilhelm von der Lieth, Thomas Lütteke, Martin Frank (eds
    01/2009; John Wiley & Sons., ISBN: 978-0-470-01667-1
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    ABSTRACT: The conformational properties of the neutral exopolysaccharide produced by Lactobacillus delbrueckii ssp. bulgaricus LBB.B26 have been studied by NMR measurements and molecular modelling. The exopolysaccharide, with an average molecular mass of 1.3 x 10(6) Da, was previously determined to consist of pentasaccharide repeating units with the following structure: -->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)-beta-d-Galf-(1-->3)-[alpha-D-Glcp-(1-->6)-]alpha-D-Galp-(1-->. Adiabatic maps were generated for each of the disaccharide fragments in the repeating unit. In addition, free energy maps calculated from MD simulations were obtained for each of the glycosidic linkages in an extended repeating unit and the influence of the Galf residue on the conformational properties of the repeating unit was investigated. The values of the global energy minima provided by the free energy maps were used to build a polymer chain. The polysaccharide was shown to have a random coil structure, without stable extended helical motifs.
    Organic & Biomolecular Chemistry 01/2009; 7(2):280-7. · 3.57 Impact Factor
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    René Ranzinger, Stephan Herget, Thomas Wetter, Claus-Wilhelm von der Lieth
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    ABSTRACT: Although carbohydrates are the third major class of biological macromolecules, after proteins and DNA, there is neither a comprehensive database for carbohydrate structures nor an established universal structure encoding scheme for computational purposes. Funding for further development of the Complex Carbohydrate Structure Database (CCSD or CarbBank) ceased in 1997, and since then several initiatives have developed independent databases with partially overlapping foci. For each database, different encoding schemes for residues and sequence topology were designed. Therefore, it is virtually impossible to obtain an overview of all deposited structures or to compare the contents of the various databases. We have implemented procedures which download the structures contained in the seven major databases, e.g. GLYCOSCIENCES.de, the Consortium for Functional Glycomics (CFG), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Bacterial Carbohydrate Structure Database (BCSDB). We have created a new database called GlycomeDB, containing all structures, their taxonomic annotations and references (IDs) for the original databases. More than 100000 datasets were imported, resulting in more than 33000 unique sequences now encoded in GlycomeDB using the universal format GlycoCT. Inconsistencies were found in all public databases, which were discussed and corrected in multiple feedback rounds with the responsible curators. GlycomeDB is a new, publicly available database for carbohydrate sequences with a unified, all-encompassing structure encoding format and NCBI taxonomic referencing. The database is updated weekly and can be downloaded free of charge. The JAVA application GlycoUpdateDB is also available for establishing and updating a local installation of GlycomeDB. With the advent of GlycomeDB, the distributed islands of knowledge in glycomics are now bridged to form a single resource.
    BMC Bioinformatics 10/2008; 9:384. · 3.02 Impact Factor
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    ABSTRACT: There are considerable differences between bacterial and mammalian glycans. In contrast to most eukaryotic carbohydrates, bacterial glycans are often composed of repeating units with diverse functions ranging from structural reinforcement to adhesion, colonization and camouflage. Since bacterial glycans are typically displayed at the cell surface, they can interact with the environment and, therefore, have significant biomedical importance. The sequence characteristics of glycans (monosaccharide composition, modifications, and linkage patterns) for the higher bacterial taxonomic classes have been examined and compared with the data for mammals, with both similarities and unique features becoming evident. Compared to mammalian glycans, the bacterial glycans deposited in the current databases have a more than ten-fold greater diversity at the monosaccharide level, and the disaccharide pattern space is approximately nine times larger. Specific bacterial subclasses exhibit characteristic glycans which can be distinguished on the basis of distinctive structural features or sequence properties. For the first time a systematic database analysis of the bacterial glycome has been performed. This study summarizes the current knowledge of bacterial glycan architecture and diversity and reveals putative targets for the rational design and development of therapeutic intervention strategies by comparing bacterial and mammalian glycans.
    BMC Structural Biology 09/2008; 8:35. · 2.10 Impact Factor
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    ABSTRACT: The activator protein-1 transcription factor is a heterodimer containing one of each of the Fos and Jun subfamilies of basic-region leucine-zipper proteins. We have previously shown by fluorescence cross-correlation spectroscopy (FCCS) that the fluorescent fusion proteins Fos-EGFP and Jun-mRFP1, cotransfected in HeLa cells, formed stable complexes in situ. Here we studied the relative position of the C-terminal domains via fluorescence resonance energy transfer (FRET) measured by flow cytometry and confocal microscopy. To get a more detailed insight into the conformation of the C-terminal domains of the complex we constructed C-terminal labeled full-length and truncated forms of Fos. We developed a novel iterative evaluation method to determine accurate FRET efficiencies regardless of relative protein expression levels, using a spectral- or intensity-based approach. The full-length C-terminal-labeled Jun and Fos proteins displayed a FRET-measured average distance of 8 +/- 1 nm. Deletion of the last 164 amino acids at the C-terminus of Fos resulted in a distance of 6.1 +/- 1 nm between the labels. FCCS shows that Jun-mRFP1 and the truncated Fos-EGFP also interact stably in the nucleus, although they bind to nuclear components with lower affinity. Thus, the C-terminal end of Fos may play a role in the stabilization of the interaction between activator protein-1 and DNA. Molecular dynamics simulations predict a dye-to-dye distance of 6.7 +/- 0.1 nm for the dimer between Jun-mRFP1 and the truncated Fos-EGFP, in good agreement with our FRET data. A wide variety of models could be developed for the full-length dimer, with possible dye-to-dye distances varying largely between 6 and 20 nm. However, from our FRET results we can conclude that more than half of the occurring dye-to-dye distances are between 6 and 10 nm.
    Biophysical Journal 05/2008; 94(7):2859-68. · 3.67 Impact Factor
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    ABSTRACT: Key issues relating to glycomics research were discussed after the workshop entitled "Frontiers in Glycomics: Bioinformatics and Biomarkers in Disease" by two focus groups nominated by the organizers. The groups focused on two themes: (i) glycomics as the new frontier for the discovery of biomarkers of disease and (ii) requirements for the development of informatics for glycomics and glycobiology. The mandate of the focus groups was to build consensus on these issues and develop a summary of findings and recommendations for presentation to the NIH and the greater scientific community. A list of scientific priorities was developed, presented, and discussed at the workshops. Additional suggestions were solicited from workshop participants and collected using the workshop mailing list. The results are summarized in this White Paper, authored by the co-chairs of the focus groups.
    PROTEOMICS 02/2008; 8(1):8-20. · 4.13 Impact Factor
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    ABSTRACT: The Human immunodeficiency virus 1 derived capsid assembly inhibitor peptide (HIV-1 CAI-peptide) is a promising lead candidate for anti-HIV drug development. Its drawback, however, is that it cannot permeate cells directly. Here we report the transport of the pharmacologically active CAI-peptide into human lymphocytes and Human Embryonic Lung cells (HEL) using the BioShuttle platform. Generally, the transfer of pharmacologically active substances across membranes, demonstrated by confocal laser scanning microscopy (CLSM), could lead to a loss of function by changing the molecule's structure. Molecular dynamics (MD) simulations and circular dichroism (CD) studies suggest that the CAI-peptide has an intrinsic capacity to form a helical structure, which seems to be critical for the pharmacological effect as revealed by intensive docking calculations and comparison with control peptides. This coupling of the CAI-peptide to a BioShuttle-molecule additionally improved its solubility. Under the conditions described, the HIV-1 CAI peptide was transported into living cells and could be localized in the vicinity of the mitochondria.
    International journal of medical sciences 02/2008; 5(5):230-9. · 2.07 Impact Factor

Publication Stats

878 Citations
163.43 Total Impact Points

Institutions

  • 1996–2010
    • German Cancer Research Center
      • Division of Radiopharmaceutical Chemistry
      Heidelburg, Baden-Württemberg, Germany
  • 2004–2008
    • Comenius University in Bratislava
      • Department of Pharmaceutical Chemistry
      Bratislava, Bratislavsky Kraj, Slovakia
  • 2002–2006
    • Ludwig-Maximilian-University of Munich
      • Faculty of Veterinary Medicine
      München, Bavaria, Germany
  • 2003
    • Universität zu Lübeck
      • Institut für Chemie
      Lübeck, Schleswig-Holstein, Germany
  • 1996–1997
    • Slovak Academy of Sciences
      • Department of Biophysics
      Presburg, Bratislavský, Slovakia