Sabine André

Ludwig-Maximilians-University of Munich, München, Bavaria, Germany

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Publications (307)1087.91 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Lectins translate information encoded in glycan chains of cellular glycoconjugates into bioeffects. The topological presentation of contact sites for cognate sugar binding is a crucial factor toward this end. To dissect the significance of such phylogenetically conserved properties, the design and engineering of non-natural variants are attractive approaches. Here, a homodimeric human lectin, i.e. adhesion/growth-regulatory galectin-1, is converted into a tandem-repeat display by introducing the 33-amino-acid linker of another family member (i.e. galectin-8). The yield of variant was reduced by about a third. This protein had ∼10-fold higher activity in hemagglutination. Nearly complete sequence determination by mass-spectrometric in-source decay and fingerprinting excluded the presence of any modifications. When 1H-15N heteronuclear single-quantum coherence data on the 15N-labeled variant and wild-type protein were compared, changes in chemical shifts, signal intensities and resonance multiplicities revealed reduction of stability of interfacial contacts between the lectin domains and an increase in inter-domain flexibility. When both binding sites in the variant were loaded with ligand, association of the two carbohydrate recognition domains was enhanced, corroborated by gel filtration. Dynamic changes in the spatial presentation of the two lectin domains in the context of a tandem-repeat display can alter counterreceptor targeting relative to the fixed positions found in the proto-type galectin homodimer.
    Protein Engineering Design and Selection 07/2015; DOI:10.1093/protein/gzv014 · 2.32 Impact Factor
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    ABSTRACT: The increasing evidence for the physiological significance of glycan-protein (lectin) interactions prompts considerations for respective bioactivity of plant polysaccharides. Arabinogalactan from larch, a polysaccharide with a β1,3-linked galactose core and branches at the 6'-hydroxyl, was thus tested, together with two processed forms treated either with oxalic or trifluoroacetic acid. Hydrolysis by acid reduced the arabinose contents without backbone degradation. The three preparations were tested as an inhibitor of lectin binding in solid-phase and cell-based assays, using the toxin from Viscum album and a panel of seven human lectins (six galectins and a C-type lectin). Increasing potency correlating with the molecular contents of galactose was seen for the plant toxin. In general, relatively weak or no inhibitory capacity was detected for the three preparations, when binding of the human galectins and avian orthologues used as controls was measured. Acid-treated polysaccharides also weakly interfered with binding of the galactose-specific C-type lectin of human macrophages. Larch arabinogalactan, tested as a model, will thus most likely not impair (ga)lectin functionality physiologically. Georg Thieme Verlag KG Stuttgart · New York.
    Planta Medica 06/2015; DOI:10.1055/s-0035-1546113 · 2.34 Impact Factor
  • Proceedings of the National Academy of Sciences 05/2015; 112(18):5585-5590. DOI:10.1073/pnas.1506220112 · 9.81 Impact Factor
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    ABSTRACT: The profile of cell surface molecules, the biochemical platform for cellular communication, can be likened to a molecular fingerprint. Historically, raising monoclonal antibodies by immunization with cells has been instrumental in obtaining tools suited for phenotyping and functional analysis. Initially for leukocyte antigens, the resulting cluster of differentiation (CD) nomenclature has become a popular system for classification. Glycans presented on proteins or lipids and receptors for carbohydrate structures (lectins) are part of the CD list. Our review presents biochemical and biomedical highlights of the respective CD entries. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Trends in Biochemical Sciences 05/2015; 40(7). DOI:10.1016/j.tibs.2015.03.013 · 13.52 Impact Factor
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    ABSTRACT: Emerging insights into the functional spectrum of tissue lectins leads to identification of new targets for the custom-made design of potent inhibitors, providing a challenge for synthetic chemistry. The affinity and selectivity of a carbohydrate ligand for a lectin may immensely be increased by a number of approaches, which includes varying geometrical or topological features. This perspective leads to the design and synthesis of glycoclusters and their testing using assays of physiological relevance. Herein, hydroquinone, resorcinol, benzene-1,3,5-triol and tetra(4-hydroxyphenyl)ethene have been employed as scaffolds and propargyl derivatives obtained. The triazole-containing linker to the alpha/beta-O/S-glycosides of GlcNAc/GalNAc presented on these scaffolds was generated by copper-catalysed azide-alkyne cycloaddition. This strategy was used to give a panel of nine glycoclusters with bi-, tri- and tetravalency. Maintained activity for lectin binding after conjugation was ascertained for both sugars in solid-phase assays with the plant agglutinins WGA (GlcNAc) and DBA (GalNAc). Absence of cross-reactivity excluded any carbohydrate-independent reactivity of the bivalent compounds, allowing to proceed to further testing with a biomedically relevant lectin specific for GalNAc. Macrophage galactose(-binding C)-type lectin, involved in immune defence by dendritic cells and in virus uptake, was produced as soluble protein without/with its alpha-helical coiled-coil stalk region. Binding to ligands presented on a matrix and on cell surfaces was highly susceptible to presence of the tetravalent inhibitor derived from the tetraphenylethene-containing scaffold, and presentation of GalNAc in an alpha-thioglycosidic linkage proved favorable. Cross-reactivity of this glycocluster to human galectins-3 and -4, which interact with Tn-antigen-presenting mucins, was rather small. Evidently, the valency and spatial display of alpha-GalNAc residues is a key factor to design potent and selective inhibitors for this lectin.
    Organic & Biomolecular Chemistry 02/2015; 13(14). DOI:10.1039/C5OB00048C · 3.49 Impact Factor
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    ABSTRACT: A major aspect of carbohydrate-dependent galectin functionality is their cross-linking capacity. Using a cell surface as biorelevant platform for galectin binding and a panel of 40 glycans as sensor part of a fluorescent polyacrylamide neoglycopolymer for profiling galectin reactivity, properties of related proteins can be comparatively analyzed. The group of the chicken galectins (CGs) is an especially suited system toward this end due to its relatively small size, compared to mammalian galectins. The experiments reveal particularly strong reactivity toward N-acetyllactosamine repeats for all tested CGs and shared reactivity of CG-1A and CG-2 to histo-blood group ABH determinants. In cross-species comparison, CG-1B's properties closely resembled those of human galectin-1, as was the case for the galectin-2 (but not galectin-3) orthologue pair. Although binding-site architectures are rather similar, reactivity patterns can well differ. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:
    Glycobiology 02/2015; 25(7). DOI:10.1093/glycob/cwv012 · 3.75 Impact Factor
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    ABSTRACT: Glycodendrimersomes with programmable surface display of glycan, together with artificially engineered galectins, were used to understand the physiological significance of human lectins with homodimeric and tandem-repeat-type displays. The mode of topological surface presentation and the density of glycan affected vesicle aggregation mediated by multivalent carbohydrate-protein interactions. The cross-linking capacity of homodimeric lectins was enhanced by covalent connection of the two carbohydrate-binding sites. These findings highlight the value of glycodendrimersomes as versatile cell membrane mimetics, and assays provide diagnostic tools for protein functionality. This work also provides guidelines for the design of cell separators, bioactive matrices, bioeffectors, and other biomedical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Angewandte Chemie International Edition in English 02/2015; 127(13). DOI:10.1002/anie.201410882 · 13.45 Impact Factor
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    ABSTRACT: The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical properties endow carbohydrates to form oligomers with unsurpassed structural variability. Owing to their capacity to engage in hydrogen (and coordination) bonding and C-H/π-interactions these "code words" can be "read" (in Latin, legere) by specific receptors. A distinct class of carbohydrate-binding proteins are the lectins. More than a dozen protein folds have developed carbohydrate-binding capacity in vertebrates. Taking galectins as an example, distinct expression patterns are traced. The availability of labeled endogenous lectins facilitates monitoring of tissue reactivity, extending the scope of lectin histochemistry beyond that which traditionally involved plant lectins. Presentation of glycan and its cognate lectin can be orchestrated, making a glycan-based effector pathway in growth control of tumor and activated T cells possible. In order to unravel the structural basis of lectin specificity for particular glycoconjugates mimetics of branched glycans and programmable models of cell surfaces are being developed by strategic combination of lectin research with synthetic and supramolecular chemistry.
    Molecules 02/2015; 20(2):1788-1823. DOI:10.3390/molecules20021788 · 2.42 Impact Factor
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    ABSTRACT: Acta Crystallographica Section F: Structural Biology Communications is a rapid all-electronic journal, which provides a home for short communications on the crystalliza-tion and structure of biological macromolecules. Structures determined through structural genomics initiatives or from iterative studies such as those used in the pharmaceutical industry are particularly welcomed. Articles are available online when ready, making publication as fast as possible, and include unlimited free colour illustrations, movies and other enhancements. The editorial process is completely electronic with respect to deposition, submission, refereeing and publication.
    Acta Crystallographica 02/2015; 71(Pt 2):184-188. DOI:10.1107/S2053230X15000023
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    ABSTRACT: The emerging significance of lectins for pathophysiological processes provides incentive for the design of potent inhibitors. To this end, systematic assessment of contributions to affinity and selectivity by distinct types of synthetic tailoring of glycosides is a salient step, here taken for the aglyconic modifications of two disaccharide core structures. Firstly we report the synthesis of seven N-linked-lactosides and of eight O-linked N-acetyllactosamines, each substituted with a 1,2,3-triazole unit, prepared by copper-catalyzed azide–alkyne cycloaddition (CuAAC). The totally regioselective β-D-(14) galactosylation of a 6-O-TBDPSi-protected N-acetylglucosamine acceptor provided efficient access to the N-acetyllactosamine precursor. The resulting compounds were then systematically tested for lectin reactivity in two binding assays of increasing biorelevance (inhibition of lectin binding to a surface-presented glycoprotein and to cell surfaces). As well as a plant toxin, we also screened the relative inhibitory potential with adhesion/growth-regulatory galectins (total of eight proteins). This type of modification yielded up to 2.5-fold enhancement for prototype proteins, with further increases for galectins-3 and -4. Moreover, the availability of 15N-labeled proteins and full assignments enabled 1H,15N HSQC-based measurements for hu- man galectins-1, -3, and -7 against p-nitrophenyl lactopyranoside, a frequently tested standard inhibitor containing an aromatic aglycone. The measurements confirmed the highest affinity against galectin-3 and detected chemical shift differences in its hydrophobic core upon ligand binding, besides common alterations around the canonical contact site for the lactoside residue. What can be accomplished in terms of affinity/selectivity by this type of core extension having been determined, the applied combined strategy should be instrumental for proceeding with defining structure–activity correlations at other bioinspired sites in glycans and beyond the tested lectin types.
    ChemBioChem 01/2015; 16(1). DOI:10.1002/cbic.201402474 · 3.06 Impact Factor
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    ABSTRACT: Substitution of the oxygen atom in the glycosidic linkage by a disulfide bond or by selenium makes the resulting glycoside resistant to hydrolysis. To clarify the consequences for affinity to lectins we prepared benzene-based mono- to trivalent dithiogalactosides. Inhibitory capacity increased with valency for a plant toxin, the synthetic compounds potently blocking its binding to a lactose-presenting matrix and to cells. Human galectins were much less sensitive to the disulfides than the toxin. This differential response constitutes a beneficial effect to avoid cross-reactivity in vivo. Symmetrical selenodigalactoside and diselenodigalactoside were prepared and similarly tested. Both compounds proved rather equally bioactive for the toxin, graded activity was measured for human galectins. This result directs attention to further studies to relate Se-dependent alterations in bond angle and length as well as van der Waals radius to binding properties of selenoglycosides to biomedically relevant lectins.
    Bioorganic & Medicinal Chemistry Letters 12/2014; 25(4). DOI:10.1016/j.bmcl.2014.12.049 · 2.33 Impact Factor
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    ABSTRACT: The human macrophage galactose-type lectin (MGL) is a key physiological receptor for the carcinoma-associated Tn antigen (GalNAc-α-1-O-Ser/Thr) in mucins. NMR and modeling-based data on the molecular recognition features of synthetic Tn-bearing glycopeptides by MGL are presented. Cognate epitopes on the sugar and matching key amino acids involved in the interaction were identified by saturation transfer difference (STD) NMR spectroscopy. Only the amino acids close to the glycosylation site in the peptides are involved in lectin contact. Moreover, control experiments with non-glycosylated MUC1 peptides unequivocally showed that the sugar residue is essential for MGL binding, as is Ca2+. NMR data were complemented with molecular dynamics simulations and Corcema-ST to establish a 3D view on the molecular recognition process between Gal, GalNAc, and the Tn-presenting glycopeptides and MGL. Gal and GalNAc have a dual binding mode with opposite trend of the main interaction pattern and the differences in affinity can be explained by additional hydrogen bonds and CH–π contacts involving exclusively the NHAc moiety.
    Chemistry - A European Journal 12/2014; 20(49). DOI:10.1002/chem.201404566 · 5.70 Impact Factor
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    ABSTRACT: Detailed comparative analysis of at first sight not related process cascades is a means toward this aim: to trace common effector mechanisms and hereby eventually inspire innovative routes for therapeutic management. Following this concept, promotion of tumor progression by stroma, especially cancer-associated fibroblasts and smooth muscle actin-positive myofibroblasts, and beneficial activity of respective cells in wound healing have helped to delineate the involvement of endogenous lectins of the family of galectins has been delineated. In addition to initiating conversion of fibroblasts to myofibroblasts, galectin-1 instructs the cells to produce a structurally complex extracellular matrix. This bioscaffold is useful for keratinocyte culture, also apparently operative in ameliorating wound healing. These functional aspects encourage to study in detail how lectin-(glycan) counterreceptor display is orchestrated. Such insights are assumed to have potential to contribute to rationally manipulate stem/precursor cells as resource in regenerative medicine.
    Histology and histopathology 10/2014; 30(3). · 2.24 Impact Factor
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    ABSTRACT: An accelerated modular synthesis produced 18 amphiphilic Janus glycodendrimers with three different topologies formed from either two or one carbohydrate head groups or a mixed constellation with a noncarbohydrate hydrophilic arm. By simple injection of their THF solutions into water or buffer, all of the Janus compounds self-assembled into uniform, stable, and soft unilamellar vesicles, denoted glycodendrimersomes. The mixed constellation topology glycodendrimersomes were demonstrated to be most efficient in binding plant, bacterial, and human lectins. This evidence with biomedically relevant receptors offers a promising perspective for the application of such glycodendrimersomes in targeted drug delivery, vaccines, and other areas of nanomedicine.
    Angewandte Chemie International Edition in English 10/2014; 53(41). DOI:10.1002/anie.201403186 · 13.45 Impact Factor
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    ABSTRACT: The physiological compound sodium butyrate can induce differentiation in colon cancer cells in vitro. Due to the role of galectins in growth control we explored its effect on this network beyond galectins-1 and -3, with deliberate consideration of the status of microsatellite stability, for nine cell lines.
    Anticancer research 10/2014; 34(10):5429-38. · 1.87 Impact Factor
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    ABSTRACT: Stromal cells in the tumor microenvironment are primarily considered as sources of promalignant factors. The objective of our study was to define the effect of extracellular matrix (ECM) produced by normal dermal or cancer-associated fibroblasts exposed to adhesion/growth-regulatory lectin galectin-1 on human umbilical vein endothelial cells (HUVECs).
    Anticancer research 08/2014; 34(8):3991-6. · 1.87 Impact Factor
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    ABSTRACT: Cancer-associated fibroblasts (CAFs) play a role in the progression of malignant tumors. They are formed by conversion of fibroblasts to smooth muscle α-actin-positive (SMA-positive) myofibroblasts. Polyamines are known to change the arrangement of the actin cytoskeleton by binding to the anionic actin. We tested the effect of the synthetic polyamine BPA-C8 on the transition of human dermal fibroblasts to myofibroblasts induced either by TGF-β1 alone or by TGF-β1 together with adhesion/growth-regulatory galectin-1. Pre-existing CAFs, myofibroblasts from pancreatitis, and rat smooth muscle cells were also exposed to BPA-C8. BPA-C8 impaired myofibroblast formation from activated fibroblasts, but it had no effect on cells already expressing SMA. BPA-C8 also reduced the occurrence of an extracellular matrix around the activated fibroblasts. The reported data thus extend current insights into polyamine activity, adding interference with tumor progression to the tumor-promoting processes warranting study.
    ChemBioChem 07/2014; 15(10). DOI:10.1002/cbic.201402087 · 3.06 Impact Factor
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    ABSTRACT: Background:The aim of this study was to characterize the immunohistochemical expression of galectin 1, 3, and 9 in normal oral epithelium, oral squamous papilloma, and oral squamous cell carcinoma.Materials and Methods:Immunohistochemical staining for galectins 1, 3, and 9 was evaluated in 8 samples of normal oral squamous epithelium, 15 samples of oral squamous papilloma, and 41 samples of oral squamous cell carcinoma. Immunohistochemical data were assessed by Kruskal-Wallis non-parametric test followed by Dunn's test. For all analyzes, it was adopted the value of P <0.05 for statistical significance.Results:Significant differences were found in galectin- 3 expression when comparing ordinary mucosa and oral squamous papilloma with the oral squamous cell carcinoma samples.Conclusion:These findings indicate that galectin-3 is closely involved in malignant transformation of oral mucosa cells.
    Dental research journal 07/2014; 11(4):508-12.
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    ABSTRACT: The apparent connection of galectin-3 to chondrocyte survival and osteoarthritis-like cartilage modifications in animal models provided incentive for the mapping of seven members of this family of adhesion/growth-regulatory proteins in human cartilage specimens. Starting with work in vitro, RT-qPCR analyses and immunocytochemistry revealed gene transcription and protein presence in cultured OA chondrocytes, especially for galectin-1, galectin-3 and galectin-8. Immunohistochemistry in clinical specimens with mild and severe cartilage degeneration detected galectins in chondrocytes-with upregulation, especially of galectin-1 in areas of severe degeneration-accompanied by α2,6-sialylation in the pericellular matrix. Given the possibility for additive/antagonistic activities between galectins, these results direct further research toward examining cellular effects of (1) these proteins (alone or in combination) on chondrocytes and (2) remodeling of the chondrocyte glycophenotype.
    Histochemie 07/2014; 142(4). DOI:10.1007/s00418-014-1234-x · 2.93 Impact Factor
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    ABSTRACT: Many human proteins have a modular design with receptor and structural domains. Using adhesion/growth-regulatory galectin-3 as model, we describe an interdisciplinary strategy to define the functional significance of its tail established by nine non-triple helical collagen-like repeats (I-IX) and the N-terminal peptide. Genetic engineering with sophisticated mass spectrometric product analysis provided the tools for biotesting, i.e. eight protein variants with different degrees of tail truncation. Evidently, different activities (cis binding and cell bridging) are affected by tail shortening in a different manner. Thus, this combined approach reveals an unsuspected complexity of structure-function relationship, encouraging further application beyond this chimera-type galectin.
    Biochimie 06/2014; 104C. DOI:10.1016/j.biochi.2014.05.010 · 3.12 Impact Factor

Publication Stats

8k Citations
1,087.91 Total Impact Points


  • 1994–2015
    • Ludwig-Maximilians-University of Munich
      • • Faculty of Veterinary Medicine
      • • Chair of Physiological Chemistry
      München, Bavaria, Germany
  • 2008–2014
    • Technische Universität München
      München, Bavaria, Germany
  • 2013
    • Universität Bern
      • Institute of Pathology
      Bern, BE, Switzerland
    • Centro de Investigaciones Biológicas
      Madrid, Madrid, Spain
    • University of Minnesota Duluth
      • Department of Chemistry and Biochemistry
      Duluth, MN, United States
  • 2011
    • Charles University in Prague
      • Anatomický ústav (1. LF)
      Praha, Hlavni mesto Praha, Czech Republic
    • Federal University of Minas Gerais
      Cidade de Minas, Minas Gerais, Brazil
    • Chang Gung University
      • College of Medicine
      Taoyuan, Taiwan, Taiwan
  • 2010
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2009
    • Henry Ford Hospital
      • Hypertension and Vascular Research Division
      Detroit, Michigan, United States
    • University College Dublin
      • Centre for Synthesis and Chemical Biology
      Dublin, Leinster, Ireland
    • Complutense University of Madrid
      • Departamento de Química Orgánica y Farmacéutica
      Madrid, Madrid, Spain
  • 2007–2009
    • Université de Mons
      • Faculty of Medicine and Pharmacy
      Mons, Walloon Region, Belgium
  • 2006
    • Institute of Physical Chemistry Rocasolano
      Madrid, Madrid, Spain
  • 2005
    • Charité Universitätsmedizin Berlin
      • Institute of Pathology
      Berlin, Land Berlin, Germany
    • Vrije Universiteit Brussel
      Bruxelles, Brussels Capital Region, Belgium
    • University of Szeged
      • Department of Surgery
      Szeged, Csongrad megye, Hungary
    • Albert Einstein College of Medicine
      • Department of Molecular Pharmacology
      New York City, NY, United States
    • University Hospital Brussels
      • Department of Neurosurgery
      Bruxelles, Brussels Capital Region, Belgium
  • 2004
    • Academy of Sciences of the Czech Republic
      • Institute of Macromolecular Chemistry
      Praha, Praha, Czech Republic
    • University of Ottawa
      • Department of Chemistry
      Ottawa, Ontario, Canada
    • Institut Jules Bordet
      Bruxelles, Brussels Capital Region, Belgium
  • 2003
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 2001
    • National Academy of Sciences of Belarus
      • Institute of Physiology
      Myenyesk, Minsk, Belarus
  • 1999
    • Belarusian State University
      • Department of Biophysics
      Minsk, Minskaya Voblasts', Belarus
  • 1998
    • Belarussian State Institute of Metrology
      Myenyesk, Minsk, Belarus