A5078008743- Proteoglycans and glycosaminoglycans research
- Chemokine receptors and signaling
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Inhalation and Respiratory Drug Delivery
- Lymphoma Diagnosis and Treatment
- Asthma and respiratory diseases
- Viral-associated cancers and disorders
- Salivary Gland Disorders and Functions
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- Fibroblast Growth Factor Research
- Eosinophilic Disorders and Syndromes
- Microencapsulation and Drying Processes
- Heparin-Induced Thrombocytopenia and Thrombosis
- Protein purification and stability
- Neonatal Respiratory Health Research
- Platelet Disorders and Treatments
- Peptidase Inhibition and Analysis
- Respiratory viral infections research
- Cutaneous lymphoproliferative disorders research
- SARS-CoV-2 detection and testing
University of Graz
2014-2025
Innovacell Biotechnologie (Austria)
2014-2019
Medical University of Graz
2010-2012
Single domain shark variable of new antigen receptor (VNAR) antibodies can offer a viable alternative to conventional Ig-based monoclonal in treating COVID-19 disease during the current pandemic. Here we report identification neutralizing single VNAR selected against severe acute respiratory syndrome coronavirus 2 spike protein derived from Wuhan variant using phage display. We identified 56 unique binding clones that exhibited high affinity and specificity protein. Of those, 10 showed an...
Introduction CXCL8, belonging to inflammatory chemokines, is expressed by various cell types and plays a key role in leukocyte trafficking during infections, processes, tissue injury tumor progression. Chemokines interact not only with G-protein coupled receptors but also glycosaminoglycans (GAGs), which are polyanionic linear polysaccharides. Chemokine-GAG interactions critical for creating localized concentration gradients, protecting chemokines from degradation, maintaining their efficacy...
Glycosaminoglycans (GAGs) are key ligands for proteins involved in physiological and pathological processes. Specific GAG-binding patterns rarely identified, with the heparin pentasaccharide as an Antithrombin-III ligand being best characterized. Generating glycan-specific antibodies is difficult due to their size, pattern dispersion, flexibility. Single-domain variable new antigen receptors (VNAR nanobodies) from nurse sharks highly soluble, stable, versatile. Their unique properties...
Abstract Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) are associated with various infectious pathogens. We analyzed the presence Chlamydia psittaci, pneumoniae, and trachomatis DNA in 47 nongastrointestinal 14 gastrointestinal MALT lymphomas, 37 nonmalignant control samples, 27 autoimmune precursor lesions by polymerase chain reaction amplification direct sequencing. In 13 (28%) were positive for C psittaci compared 4 (11%) samples (P = .09). was detected at...
Chemokine binding to glycosaminoglycans (GAGs) is recognised be an important step in inflammation and other pathological disorders like tumor growth metastasis. Although different ways strategies interfere with these interactions are being pursued, no major breakthrough the development of glycan-targeting drugs has been reported so far. We have engineered CXCL8 towards a dominant-negative form this chemokine (dnCXCL8) which was shown highly active various inflammatory animal models due its...
IL (interleukin)-8 [CXCL8 (CXC chemokine ligand 8)] exerts its role in inflammation by triggering neutrophils via specific GPCRs (G-protein-coupled receptors), CXCR1 receptor 1) and CXCR2, for which additional binding to endothelial HS-GAGs (heparan sulphate-glycosaminoglycans) is required. We present here a novel approach blocking the CXCL8-related inflammatory cascade generating dominant-negative CXCL8 mutants with improved GAG-binding affinity knocked-out CXCR1/CXCR2 activity. These...
As with many other pathogens, SARS-CoV-2 cell infection is strongly dependent on the interaction of virus-surface Spike protein glycosaminoglycans target cells. The glycoprotein was previously shown to interact cell-surface-exposed heparan sulfate and heparin in vitro. With aim using Enoxaparin as a treatment for COVID-19 patients prophylaxis prevent interpersonal viral transmission, we investigated GAG binding full-length protein, well its receptor domain (RBD) solution by isothermal...
Chemokines like CCL2 mediate leukocyte migration to inflammatory sites by binding G-protein coupled receptors on the target cell as well glycosaminoglycans (GAGs) endothelium of inflamed tissue. We have recently shown that dominant-negative Met-CCL2 mutant Y13A/S21K/Q23R with improved GAG affinity is highly bio-active in several animal models diseases. For chronic indications, we performed here a fusion human serum albumin (HSA) order extend half-life chemokine mutant. To compensate...
The successful substitution of complex physiological fluids, such as human saliva, remains a major challenge in drug development. Although there are large number saliva substitutes on the market, their efficacy is often inadequate due to short residence time mouth, unpleasant mouthfeel, or insufficient protection teeth. Therefore, systems need be identified that mimic functions particular salivary mucin MUC5B and unique properties saliva. To this end, plant extracts known contain...
Summary Background To recruit leucocytes to an inflammatory site, chemokine binding glycosaminoglycans ( GAG s) is critical. Therefore, strategies interfere with this interaction, aiming at the production of anti‐inflammatory agents, were developed. These include modified chemokines without affinity for G protein‐coupled receptors but enhanced s. Such compete functional binding, prevent immobilization and presentation, inhibit leucocyte migration. In addition chemokines, a ‐binding peptide...
Although glycosaminoglycan (GAG)-protein interactions are important in many physiological and pathological processes, the structural requirements for binding poorly defined. Starting with GAG-binding peptide CXCL9(74-103), peptides were designed to elucidate contribution affinity of different: (1) motifs (i.e., BBXB BBBXXB); (2) amino acids linker sequences; (3) numbers motifs. The eight chemically synthesized various GAGs was determined by isothermal fluorescence titration (IFT). Moreover,...
The role of glycosaminoglycans on the surface immune cells has so far been less studied compared to their participation in inflammatory responses as members endothelium and extracellular matrix. In this study we have therefore investigated if act concert with GPC receptors (i.e. both being cis-located leukocytes) chemokine-induced leukocyte mobilisation. For purpose, freshly-prepared human neutrophils monocytes were treated heparinase III or chondroitinase ABC digest heparan sulfate -chains...
Spray-dried products, such as synthetic peptides and hormones, have already been approved by the U.S. Food Drug Agency European Medicines Agency, while spray-dried antibodies or interleukins, are not yet available on market. Concerning latter group, knowledge whether how spray-drying (SD) can be performed without adversely affecting their biological activity is lacking. Accordingly, this study aimed at establishing a SD process (Büchi B-90 spray dryer) using three Interleukin-8 based...
Tenascin-C (TNC) is a complex glycoprotein of the extracellular matrix (ECM) involved in plethora (patho-)physiological processes, such as oncogenesis and inflammation. Since chemokines play an essential role both disease we have investigated here binding TNC to some key chemokines, namely CCL2, CCL26, CXCL8, CXCL10, CXCL12. Thereby, differential chemokine-TNC pattern was observed, with CCL26 exhibiting highest CCL2 lowest affinity for TNC. Heparan sulfate (HS), another member ECM, proved be...
Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) receptor 3 on surface eosinophilic cells. Here we have investigated role glycosaminoglycans (GAGs) as potential co-receptors in process CCL26-induced eosinophil chemotaxis. For this purpose, first identified GAG-binding site CCL26 a site-directed mutagenesis approach form an alanine screening. A panel GAG-binding-deficient...
Glycosaminoglycans are a class of linear, highly negatively charged, O-linked polysaccharides that involved in many (patho)physiological processes. In vitro experimental investigations such processes typically involve porcine-derived heparan sulfate (HS). Structural information about human, particularly organ-specific sulfate, and how it compares with HS from other organisms, is very limited. this study, was isolated human lung tissues derived five donors characterized for their overall size...
Abstract The chemokine CXCL10 is released by a plethora of cells, including immune and metastatic cancer following stimulation with interferon-gamma. It acts via its GPC receptor on T-cells attracting them to various target tissues. Glycosaminoglycans (GAGs) are regarded as co-receptors chemokines, which enable the establishment chemotactic gradient for cell migration. We have engineered human towards improved T-cell mobilisation implementing single site-directed mutation N20K into protein,...