Inhibitors for Allergic Reactions to Peanuts and Drugs: Epitope Analysis, Molecule Design and Characterization

This dissertation describes the design, synthesis and characterization of a novel type of molecule for the inhibition of allergic reactions to food proteins and drug molecules. Allergies are a growing problem in the western world, causing a person’s immune system to attack innocuous compounds such as food, environmental factors or drugs. Moreover, allergies do not have a preventative treatment that works for severe reactions. By targeting the immune proteins responsible for triggering allergic responses, immunoglobulin E molecules (IgE), in a specific manner, allergies can be prevented prior to reactions.

The process of designing these inhibitors requires first to identify the IgEs responsible for triggering allergic reactions to an allergen. We developed a novel nanoparticle based platform, we call nanoallergens, for identifying the IgEs and the regions of the allergens they react against, called epitopes. We characterized this platform in chapter 2 using small molecules and used them to identify the major epitopes of peanut allergen proteins. Next, we developed a new inhibitor design called covalent heterobivalent inhibitors (cHBI). These molecules can permanently inhibit allergy reactive IgEs and therefore prevent allergic reactions. We characterized these molecules in chapter 3 by demonstrating their effectiveness in preventing allergic reactions to small molecule drugs. Finally we used the epitope analysis from chapter 2 and the inhibitor design from chapter 3 and designed cHBIs specific to peanut allergens and used them to prevent allergic reactions to peanuts. This is a working example of how this technique can be applied to formulate inhibitors for any allergy.