(228eo) Inhibitors for Allergic Reactions to Drugs and Other Small Molecules

Penicillin is one of the most influential compounds in the history of human healthcare and it saves countless lives a year, but this drug is not always a suitable choice. For penicillin and countless other drugs that are heavily relied upon in healthcare, allergic responses are a constant concern that restricts their usage. In particular, type I hypersensitivity reactions, also known as Immunoglobulin E (IgE) mediated hypersensitivities, are the most problematic due to their ability to cause life-threatening anaphylaxis reactions. During these reactions, allergen specific IgE molecules crosslink when exposed to a carrier protein that has been conjugated with several drug molecules, triggering mast cell degranulation and therefore allergy symptoms. Our laboratory has developed targeted inhibitor molecules that specifically bind allergen specific IgEs monovalently, and thereby prevent any crosslinking from drug haptenized proteins, consequently preventing type I hypersensitivity reactions. We engineered a versatile molecular design that can potentially be adaptable in the synthesis of inhibitors for any drug or small molecule allergens. We used the design to synthesize inhibitors for penicillin G and dansyl chloride. Here, we have demonstrate that these molecules are specific only to their target IgE, form long lasting interactions, and prevent cellular degranulation from haptenized proteins both in vitro and in vivo. These inhibitors will potentially prevent life-threatening allergic reactions to drugs, and improve patient outcome.