The allergic response is controlled primarily via IL-4 mediated expression of the IgE antibody. To prevent this reaction in non-threatening instances, we propose the development of a drug capable of binding the IL-4 receptor to preclude IL-4 binding, halting downstream actions. The development of the drug will be accomplished using molecular modeling to determine lead compounds, followed by the creation of a combinatorial library capable of randomizing six functional groups on the surface of the small molecule scaffold. The binding of these scaffolds to the IL-4 receptor will be monitored via mass spec analysis and surface plasmon resonance - high affinity compounds can be further explored to optimize binding to compete with IL-4 for the receptor binding site. Concurrently, the responsiveness of these scaffolds to the biological surroundings will be improved via introduction of a second binding site within the core of the scaffold. Binding of histamine, an important mediator of the allergic response, in this second site will be a necessary first step to activate the drug to bind the IL-4 receptor, preventing further expression of IgE. The successful regulation of IL-4 receptor binding using histamine as a mediator introduces the possibility of self-medicating drugs.
