Design of Glycoengineered IL-4 Antagonists Employing Chemical and Biosynthetic Glycosylation

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 IgE. Antibodies of this type activate mast cells and basophilic eosinophilic granulocytes, which release pro-inflammatory mediators accounting for the typical symptoms IL-13 are thus major targets pharmaceutical intervention strategies treat Besides neutralizing antibodies against IL-4, IL-13, or its receptors, antagonists can present valuable alternatives. Pitrakinra, an Escherichia coli-derived antagonist, has been evaluated clinical trials asthma treatment past; however, deficits such as short serum lifetime potential immunogenicity among others stopped development. To overcome deficits, PEGylation therapeutically important proteins used increase proteolytic stability. As alternative, glycoengineering is emerging strategy improve pharmacokinetics protein therapeutics. In study, we have established different attach glycan moieties defined positions IL-4. Different chemical attachment employing thiol chemistry were glucose molecule at amino acid position 121, converting into highly effective antagonist. enhance stability additional structures introduced by utilizing eucaryotic expression. combination biosynthetic could be useful therapeutic alternatives already