Covalent Heterobivalent Inhibitor Design for Inhibition of IgE-Dependent Penicillin Allergy in a Murine Model.

ABSTRACT: Drug allergies occur when hapten-like drug metabolites conjugated to serum proteins, through their interactions with specific IgE, trigger allergic reactions that can be life threatening. A molecule termed covalent heterobivalent inhibitor (cHBI) was designed to specifically target drug hapten-specific IgE to prevent it from binding drug-haptenated serum proteins. cHBI binds the two independent sites on a drug hapten-specific Ab and covalently conjugates only to the specific IgE, permanently inhibiting it. The cHBI design was evaluated via ELISA to measure cHBI-IgE binding, degranulation assays of rat basophil leukemia cells for in vitro efficacy, and mouse models of ear swelling and systemic anaphylaxis responses for in vivo efficacy. The cHBI design was evaluated using two separate model

SUBMITTER: Deak PE 

PROVIDER: S-EPMC6823631 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature