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

<p>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. </p><p>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.</p>