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Author Andreas J Kungl

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Single domain shark VNAR antibodies neutralize SARS-CoV-2 infection in vitro.

Aziz Gauhar, Cyril V Privezentzev, Mykhaylo Demydchuk, Tanja Gerlza, Julia Rieger, Andreas J Kungl, Frank S Walsh, J Lynn Rutkowski, Pawel Stocki,

Single domain shark variable domain of new antigen receptor (VNAR) antibodies can offer a viable alternative to conventional Ig-based monoclonal antibodies in treating COVID-19 disease during the current pandemic. Here we report the identification of neutralizing single domain VNAR antibodies selected against the severe acute respiratory syndrome coronavirus 2 spike ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(11):e21970]

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Isolation and Characterization of Heparan Sulfate from Human Lung Tissues.

Rupert Derler, Nikola Kitic, Tanja Gerlza, Andreas J Kungl,

Glycosaminoglycans are a class of linear, highly negatively charged, <i>O</i>-linked polysaccharides that are involved in many (patho)physiological processes. In vitro experimental investigations of such processes typically involve porcine-derived heparan sulfate (HS). Structural information about human, particularly organ-specific heparan sulfate, and how it compares with HS from other organisms, is very ... Read more >>

Molecules (Molecules (Basel, Switzerland))
[2021, 26(18):]

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Inhibition of Drug-Induced Liver Injury in Mice Using a Positively Charged Peptide That Binds DNA.

Pedro E Marques, Sofie Vandendriessche, Thiago H C de Oliveira, Helena Crijns, Mateus E Lopes, Marfa Blanter, Sara Schuermans, Karen Yu, Fariba Poosti, Vincent Vanheule, Rik Janssens, Daiane Boff, Andreas J Kungl, Gustavo B Menezes, Mauro M Teixeira, Paul Proost,

Hepatic cell death occurs in response to diverse stimuli such as chemical and physical damage. The exposure of intracellular contents such as DNA during necrosis induces a severe inflammatory response that has yet to be fully explored therapeutically. Here, we sought means to neutralize the ability of extracellular DNA to ... Read more >>

Hepatol Commun (Hepatology communications)
[2021, 5(10):1737-1754]

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Development of Molecules Antagonizing Heparan Sulfate Proteoglycans.

Tanja Gerlza, Christina Trojacher, Nikola Kitic, Tiziana Adage, Andreas J Kungl,

Heparan sulfate proteoglycans (HSPGs) occur in almost every tissue of the human body and consist of a protein core, with covalently attached glycosaminoglycan polysaccharide chains. These glycosaminoglycans are characterized by their polyanionic nature, due to sulfate and carboxyl groups, which are distributed along the chain. These chains can be modified ... Read more >>

Semin Thromb Hemost (Seminars in thrombosis and hemostasis)
[2021, 47(3):316-332]

Cited: 0 times

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Cytokines and Chemokines in SARS-CoV-2 Infections-Therapeutic Strategies Targeting Cytokine Storm.

Alexandra Pum, Maria Ennemoser, Tiziana Adage, Andreas J Kungl,

The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and ... Read more >>

Biomolecules (Biomolecules)
[2021, 11(1):]

Cited: 10 times

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Structural Fuzziness of the RNA-Organizing Protein SERF Determines a Toxic Gain-of-interaction.

N Helge Meyer, Hanna Dellago, Carmen Tam-Amersdorfer, David A Merle, Rosanna Parlato, Bernd Gesslbauer, Johannes Almer, Martha Gschwandtner, A Leon, Titus M Franzmann, Johannes Grillari, Andreas J Kungl, Klaus Zangger, S Fabio Falsone,

The mechanisms by which protein complexes convert from functional to pathogenic are the subject of intensive research. Here, we report how functionally unfavorable protein interactions can be induced by structural fuzziness, i.e., by persisting conformational disorder in protein complexes. We show that extreme disorder in the bound state transforms the ... Read more >>

J Mol Biol (Journal of molecular biology)
[2020, 432(4):930-951]

Cited: 4 times

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Increased Aggregation Tendency of Alpha-Synuclein in a Fully Disordered Protein Complex.

David A Merle, Anja Witternigg, Carmen Tam-Amersdorfer, Christoph Hartlmüller, Emil Spreitzer, Evelyne Schrank, Sabine Wagner-Lichtenegger, Oliver Werzer, Klaus Zangger, Andreas J Kungl, Tobias Madl, N Helge Meyer, S Fabio Falsone,

The recent discovery of biologically active fully disordered, so called random fuzzy protein-protein interactions leads to the question of how the high flexibility of these protein complexes correlates to aggregation and pathologic misfolding. We identify the structural mechanism by which a random fuzzy protein complex composed of the intrinsically disordered ... Read more >>

J Mol Biol (Journal of molecular biology)
[2019, 431(14):2581-2598]

Cited: 3 times

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Molecular dynamics simulations of the chemokine CCL2 in complex with pull down-derived heparan sulfate hexasaccharides.

Sophie Winkler, Rupert Derler, Bernd Gesslbauer, Elmar Krieger, Andreas J Kungl,

<h4>Background</h4>Binding of chemokines to glycosaminoglycans (GAGs) is a crucial step in leukocyte recruitment to inflamed tissues.<h4>Methods</h4>A disaccharide compositional analysis of the HS dp6 fraction in combination with MS analysis of the CCL2-depleted dp6 fraction was the basis for target GAG ligand structure suggestions. Four experimentally-derived heparan sulfate hexasaccharides, two potentially ... Read more >>

Biochim Biophys Acta Gen Subj (Biochimica et biophysica acta. General subjects)
[2019, 1863(3):528-533]

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Therapeutic strategies to target microbial protein-glycosaminoglycan interactions.

Johannes Almer, Bernd Gesslbauer, Andreas J Kungl,

Glycans are involved in a plethora of human pathologies including infectious diseases. Especially, glycosaminoglycans (GAGs), like heparan sulfate and chondroitin sulfate, have been found to be involved in different crucial stages of microbial invasion. Here, we review various therapeutic approaches, which target the interface of host GAGs and microbial proteins ... Read more >>

Biochem Soc Trans (Biochemical Society transactions)
[2018, 46(6):1505-1515]

Cited: 2 times

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Anti-inflammatory effects of the GAG-binding CXCL9(74-103) peptide in dinitrofluorobenzene-induced contact hypersensitivity in mice.

Vincent Vanheule, Helena Crijns, Fariba Poosti, Pieter Ruytinx, Nele Berghmans, Tanja Gerlza, Isabelle Ronsse, Noëmie Pörtner, Patrick Matthys, Andreas J Kungl, Ghislain Opdenakker, Sofie Struyf, Paul Proost,

<h4>Background</h4>To recruit leucocytes to an inflammatory site, chemokine binding to glycosaminoglycans (GAGs) is critical. Therefore, strategies to interfere with this interaction, aiming at the production of anti-inflammatory agents, were developed. These include production of modified chemokines without affinity for G protein-coupled receptors but with enhanced affinity for GAGs. Such modified ... Read more >>

Clin Exp Allergy (Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology)
[2018, 48(10):1333-1344]

Cited: 2 times

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Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis.

Emily F McNaughton, Andrew D Eustace, Sophie King, Richard B Sessions, Alasdair Kay, Michele Farris, Robert Broadbridge, Oksana Kehoe, Andreas J Kungl, Jim Middleton,

Inflammation is characterized by the infiltration of leukocytes from the circulation and into the inflamed area. Leukocytes are guided throughout this process by chemokines. These are basic proteins that interact with leukocytes to initiate their activation and extravasation via chemokine receptors. This is enabled through chemokine immobilization by glycosaminoglycans (GAGs) ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2018, 200(9):3201-3217]

Cited: 7 times

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CXCL9-Derived Peptides Differentially Inhibit Neutrophil Migration In Vivo through Interference with Glycosaminoglycan Interactions.

Vincent Vanheule, Daiane Boff, Anneleen Mortier, Rik Janssens, Björn Petri, Elzbieta Kolaczkowska, Paul Kubes, Nele Berghmans, Sofie Struyf, Andreas J Kungl, Mauro Martins Teixeira, Flavio Almeida Amaral, Paul Proost,

Several acute and chronic inflammatory diseases are driven by accumulation of activated leukocytes due to enhanced chemokine expression. In addition to specific G protein-coupled receptor-dependent signaling, chemokine-glycosaminoglycan (GAG) interactions are important for chemokine activity <i>in vivo</i>. Therefore, the GAG-chemokine interaction has been explored as target for inhibition of chemokine activity. ... Read more >>

Front Immunol (Frontiers in immunology)
[2017, 8:530]

Cited: 14 times

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Glycosaminoglycans are important mediators of neutrophilic inflammation in vivo.

Martha Gschwandtner, Elisabeth Strutzmann, Mauro M Teixeira, Hans J Anders, Maria Diedrichs-Möhring, Tanja Gerlza, Gerhild Wildner, Remo C Russo, Tiziana Adage, Andreas J Kungl,

The pro-inflammatory chemokine interleukin-8 (CXCL8) exerts its function by establishing a chemotactic gradient in infected or damaged tissues to guide neutrophil granulocytes to the site of inflammation via its G protein-coupled receptors (GPCRs) CXCR1 and CXCR2 located on neutrophils. Endothelial glycosaminoglycans (GAGs) have been proposed to support the chemotactic gradient ... Read more >>

Cytokine (Cytokine)
[2017, 91:65-73]

Cited: 9 times

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Profiling the Membrane and Glycosaminoglycan-Binding Proteomes of Moraxella catarrhalis.

Anita Karner, Bernd Gesslbauer, Anton Spreitzer, Johannes Almer, Margarita Smidt, Wolfgang Schüler, Berthold Fartmann, Wolfgang Zimmermann, Andreas Meinke, Andreas J Kungl,

Moraxella catarrhalis, a Gram-negative bacterium, is an important respiratory pathogen causing acute otitis media and exacerbations of chronic obstructive pulmonary disease. Adhesion of the pathogen to human epithelial cells is mediated via bacterial membrane adhesin proteins. To identify the surface proteome of Moraxella catarrhalis, we applied different membrane protein extraction ... Read more >>

J Proteome Res (Journal of proteome research)
[2016, 15(9):3055-3097]

Cited: 0 times

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Interfering with the CCL2-glycosaminoglycan axis as a potential approach to modulate neuroinflammation.

Martha Gschwandtner, Anna Maria Piccinini, Tanja Gerlza, Tiziana Adage, Andreas J Kungl,

Multiple Sclerosis, a chronic inflammatory demyelinating disease of the central nervous system, involves an increased expression of monocyte chemotactic protein 1 MCP1-/CCL2. For exerting its chemotactic effects, chemokine binding to glycosaminoglycans (GAGs) is required and therefore this interaction represents a potential target for therapeutic intervention. We have designed an anti-inflammatory ... Read more >>

Neurosci Lett (Neuroscience letters)
[2016, 626:164-173]

Cited: 9 times

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Exploring the glycosaminoglycan-protein interaction network by glycan-mediated pull-down proteomics.

Bernd Gesslbauer, Rupert Derler, Claudia Handwerker, Elisabeth Seles, Andreas J Kungl,

Glycosaminoglycans (GAGs) are linear, highly sulfated polysaccharides expressed by almost all animal cells. They occur as soluble molecules, or form proteoglycans by being O-linked to different core proteins on the cell surface and in the extracellular matrix. Due to their ability to interact with diverse proteins and to modulate their ... Read more >>

Electrophoresis (Electrophoresis)
[2016, 37(11):1437-1447]

Cited: 6 times

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Preparation and Characterization of Glycosaminoglycan Chemokine Coreceptors.

Nikola Kitic, Martha Gschwandtner, Rupert Derler, Tanja Gerlza, Andreas J Kungl,

Interactions between chemokines and glycosaminoglycans (GAGs) are crucial for the physiological and pathophysiological activities of chemokines. GAGs are therefore commonly designated as chemokine coreceptors which are deeply involved in the chemokine-signaling network. Studying the interaction of chemokines with GAGs is therefore a major prerequisite to fully understand the biological function ... Read more >>

Methods Enzymol (Methods in enzymology)
[2016, 570:517-538]

Cited: 0 times

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Glycosaminoglycan silencing by engineered CXCL12 variants.

Martha Gschwandtner, Martin U Trinker, Bianca Hecher, Tiziana Adage, Simi Ali, Andreas J Kungl,

We have engineered GPCR (G protein-coupled receptor) knock-out and high GAG-binding affinity into CXCL12α to inhibit CXCL12α-induced cell migration. Compared to wtCXCL12, the mutant CXCL12α (Δ8 L29K V39K) exhibited a 5.6-fold and a 2.2-fold affinity increase for heparin and heparan sulfate, respectively. From NaCl-based heparin displacement chromatography we concluded that ... Read more >>

FEBS Lett (FEBS letters)
[2015, 589(19 Pt B):2819-2824]

Cited: 4 times

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PA401, a novel CXCL8-based biologic therapeutic with increased glycosaminoglycan binding, reduces bronchoalveolar lavage neutrophils and systemic inflammatory markers in a murine model of LPS-induced lung inflammation.

Tiziana Adage, Francesca Del Bene, Francesco Fiorentini, Robert P Doornbos, Christina Zankl, Michael R Bartley, Andreas J Kungl,

<h4>Rationale</h4>Neutrophils play a fundamental role in a number of chronic lung diseases. Among the mediators of their recruitment to the lung, CXCL8 (IL-8) is considered to be one of the major players. CXCL8 exerts its chemotactic activity by binding to its GPCR receptors (CXCR1/R2) located on neutrophils, as well as ... Read more >>

Cytokine (Cytokine)
[2015, 76(2):433-441]

Cited: 9 times

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The Positively Charged COOH-terminal Glycosaminoglycan-binding CXCL9(74-103) Peptide Inhibits CXCL8-induced Neutrophil Extravasation and Monosodium Urate Crystal-induced Gout in Mice.

Vincent Vanheule, Rik Janssens, Daiane Boff, Nikola Kitic, Nele Berghmans, Isabelle Ronsse, Andreas J Kungl, Flavio Almeida Amaral, Mauro Martins Teixeira, Jo Van Damme, Paul Proost, Anneleen Mortier,

The ELR(-)CXC chemokine CXCL9 is characterized by a long, highly positively charged COOH-terminal region, absent in most other chemokines. Several natural leukocyte- and fibroblast-derived COOH-terminally truncated CXCL9 forms missing up to 30 amino acids were identified. To investigate the role of the COOH-terminal region of CXCL9, several COOH-terminal peptides were ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2015, 290(35):21292-21304]

Cited: 27 times

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Designing a mutant CCL2-HSA chimera with high glycosaminoglycan-binding affinity and selectivity.

Tanja Gerlza, Sophie Winkler, Aid Atlic, Christina Zankl, Viktoria Konya, Nikola Kitic, Elisabeth Strutzmann, Kerstin Knebl, Tiziana Adage, Akos Heinemann, Roland Weis, Andreas J Kungl,

Chemokines like CCL2 mediate leukocyte migration to inflammatory sites by binding to G-protein coupled receptors on the target cell as well as to glycosaminoglycans (GAGs) on the endothelium of the inflamed tissue. We have recently shown that the dominant-negative Met-CCL2 mutant Y13A/S21K/Q23R with improved GAG binding affinity is highly bio-active ... Read more >>

Protein Eng Des Sel (Protein engineering, design & selection : PEDS)
[2015, 28(8):231-240]

Cited: 4 times

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A combinatorial approach to biophysically characterise chemokine-glycan binding affinities for drug development.

Tanja Gerlza, Bianca Hecher, Dalibor Jeremic, Thomas Fuchs, Martha Gschwandtner, Angelika Falsone, Bernd Gesslbauer, Andreas J Kungl,

Chemokine binding to glycosaminoglycans (GAGs) is recognised to be an important step in inflammation and other pathological disorders like tumor growth and metastasis. Although different ways and strategies to interfere with these interactions are being pursued, no major breakthrough in the development of glycan-targeting drugs has been reported so far. ... Read more >>

Molecules (Molecules (Basel, Switzerland))
[2014, 19(7):10618-10634]

Cited: 18 times

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Targeting glycosaminoglycans in the lung by an engineered CXCL8 as a novel therapeutic approach to lung inflammation.

Tiziana Adage, Viktoria Konya, Corinna Weber, Elisabeth Strutzmann, Thomas Fuchs, Christina Zankl, Tanja Gerlza, Dalibor Jeremic, Akos Heinemann, Andreas J Kungl,

It is broadly recognized that chemokine-activated neutrophils play a crucial role in the inflammation and disruption of lung tissue observed in several acute and chronic lung diseases. Since glycosaminoglycan side chains of proteoglycans act as chemokine co-receptors in inflammation, we have used a CXCL8-based dominant-negative mutant, dnCXCL8, to displace neutrophil-related ... Read more >>

Eur J Pharmacol (European journal of pharmacology)
[2015, 748:83-92]

Cited: 8 times

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The effect of the decoy molecule PA401 on CXCL8 levels in bronchoalveolar lavage fluid of patients with cystic fibrosis.

Oliver J McElvaney, Niamh O'Reilly, Michelle White, Noreen Lacey, Kerstin Pohl, Tanja Gerlza, David A Bergin, Hilary Kerr, Cormac McCarthy, M Emmet O'Brien, Tiziana Adage, Andreas J Kungl, Emer P Reeves, Noel G McElvaney,

<h4>Background</h4>The chemokine interleukin-8 (CXCL8) is a key mediator of inflammation in airways of patients with cystic fibrosis (CF). Glycosaminoglycans (GAGs) possess the ability to influence the chemokine profile of the CF lung by binding CXCL8 and protecting it from proteolytic degradation. CXCL8 is maintained in an active state by this ... Read more >>

Mol Immunol (Molecular immunology)
[2015, 63(2):550-558]

Cited: 10 times

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Designing CXCL8-based decoy proteins with strong anti-inflammatory activity in vivo.

Angelika Falsone, Veronica Wabitsch, Elena Geretti, Heide Potzinger, Tanja Gerlza, James Robinson, Tiziana Adage, Mauro M Teixeira, Andreas J Kungl,

IL (interleukin)-8 [CXCL8 (CXC chemokine ligand 8)] exerts its role in inflammation by triggering neutrophils via its specific GPCRs (G-protein-coupled receptors), CXCR1 (CXC chemokine receptor 1) and CXCR2, for which additional binding to endothelial HS-GAGs (heparan sulphate-glycosaminoglycans) is required. We present here a novel approach for blocking the CXCL8-related inflammatory ... Read more >>

Biosci Rep (Bioscience reports)
[2013, 33(5):]

Cited: 13 times

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