Refine
Has Fulltext
- yes (12)
Is part of the Bibliography
- yes (12)
Document Type
- Journal article (12)
Language
- English (12)
Keywords
- Acromesomelic dysplasias (1)
- Apoptosis (1)
- Arabidopsis (1)
- BMP antagonist (1)
- BMPR1B (1)
- Bone morphogenetic protein-2 (1)
- CYR61 (1)
- Cancer (1)
- Dionaea muscipula (1)
- Grebe dysplasia (1)
- IL-4 antagonists (1)
- Interleukin-4 (IL-4) (1)
- Mechanisms (1)
- Myofibroblast differentiation (1)
- NMR spectroscopy (1)
- Physiologische Chemie (1)
- Proliferation (1)
- Receptor (1)
- Smooth-muscle-cells (1)
- T cells (1)
- T-cells (1)
- TGF-beta (1)
- TGF-β superfamily (1)
- TGFβ/BMP signaling (1)
- TGN1412 (1)
- Venusfliegenfalle (1)
- Wnt signaling cascade (1)
- antagonists (1)
- antigen binding antibody fragment (Fab) (1)
- atopic dermatitis (1)
- atopic diseases (1)
- betaglycan (1)
- binding analysis (1)
- biological locomotion (1)
- biosynthetic glycosylation (1)
- bone morphogenetic proteins (1)
- cell binding assay (1)
- cell differentiation (1)
- chemical glycosylation (1)
- cholera (1)
- chondrodysplasia (1)
- coreceptor (1)
- cytokine release (1)
- cytokines (1)
- du Pan dysplasia (1)
- expression (1)
- gene expression (1)
- glycoengineering (1)
- glycoprotein (1)
- grebe (1)
- growth factor beta (1)
- human interleukin-4 (1)
- immune evasion (1)
- jasmonic acid biosynthesis (1)
- ligand binding (1)
- ligand-receptor promiscuity (1)
- linkage analysis (1)
- luciferase (1)
- missense (1)
- mutagenesis (1)
- osteoblasts (1)
- oxazolone colitis (1)
- polymerization (1)
- protein-1 CDMP1 gene (1)
- protein-protein recognition (1)
- proteins (1)
- receptor type III (1)
- regulatory T cells (1)
- responses (1)
- rheumatoid arthritis (1)
- sequence motif analysis (1)
- signal inhibition (1)
- signal specification (1)
- signal transduction (1)
- small interfering RNAs (1)
- specificity (1)
- superfamily (1)
- tool (1)
- toxins (1)
- transporters (1)
- von Willebrand type C domain (1)
Institute
- Julius-von-Sachs-Institut für Biowissenschaften (10)
- Theodor-Boveri-Institut für Biowissenschaften (4)
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (3)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (1)
- Augenklinik und Poliklinik (1)
- Institut für Physikalische und Theoretische Chemie (1)
- Institut für Virologie und Immunbiologie (1)
- Rudolf-Virchow-Zentrum (1)
Sonstige beteiligte Institutionen
Interleukin-4 (IL-4) plays a key role in atopic diseases. It coordinates T-helper cell differentiation to subtype 2, thereby directing defense toward humoral immunity. Together with Interleukin-13, IL-4 further induces immunoglobulin class switch to IgE. Antibodies of this type activate mast cells and basophilic and eosinophilic granulocytes, which release pro-inflammatory mediators accounting for the typical symptoms of atopic diseases. IL-4 and IL-13 are thus major targets for pharmaceutical intervention strategies to treat atopic diseases. Besides neutralizing antibodies against IL-4, IL-13, or its receptors, IL-4 antagonists can present valuable alternatives. Pitrakinra, an Escherichia coli-derived IL-4 antagonist, has been evaluated in clinical trials for asthma treatment in the past; however, deficits such as short serum lifetime and potential immunogenicity among others stopped further development. To overcome such deficits, PEGylation of therapeutically important proteins has been used to increase the lifetime and proteolytic stability. As an alternative, glycoengineering is an emerging strategy used to improve pharmacokinetics of protein therapeutics. In this study, we have established different strategies to attach glycan moieties to defined positions in IL-4. Different chemical attachment strategies employing thiol chemistry were used to attach a glucose molecule at amino acid position 121, thereby converting IL-4 into a highly effective antagonist. To enhance the proteolytic stability of this IL-4 antagonist, additional glycan structures were introduced by glycoengineering utilizing eucaryotic expression. IL-4 antagonists with a combination of chemical and biosynthetic glycoengineering could be useful as therapeutic alternatives to IL-4 neutralizing antibodies already used to treat atopic diseases.