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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Covalent Heterobivalent Inhibitor Design for Inhibition of IgE-Dependent Penicillin Allergy in a Murine Model
The Journal of immunology (1950), v 203(1), pp 21-30
01 Jul 2019
PMID: 31101666
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 models: one specific to inhibit penicillin G-reactive IgE and another to inhibit IgE specific to a model compound, dansyl. We show that cHBI conjugated specifically to its target Ab and inhibited degranulation in cellular degranulation assays using rat basophil leukemia cells. Furthermore, cHBIs demonstrated in vivo inhibition of allergic responses in both murine models. We establish the cHBI design to be a versatile platform for inhibiting hapten/IgE interactions, which can potentially be applied to inhibit IgE-mediated allergic reactions to any drug/small-molecule allergy.
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Details
- Title
- Covalent Heterobivalent Inhibitor Design for Inhibition of IgE-Dependent Penicillin Allergy in a Murine Model
- Creators
- Peter E Deak - University of Notre DameBaksun Kim - University of Notre DameByunghee Koh - Indiana UniversityAmina Abdul Qayum - Indiana UniversityTanyel Kiziltepe - University of Notre DameMark H Kaplan - Indiana UniversityBasar Bilgicer - University of Notre Dame
- Publication Details
- The Journal of immunology (1950), v 203(1), pp 21-30
- Publisher
- American Association of Immunologists (AAI)
- Grant note
- R01 AI108884 / NIAID NIH HHS U54 DK106846 / NIDDK NIH HHS T32 DK007519 / NIDDK NIH HHS P30 CA082709 / NCI NIH HHS R01 AI129241 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000471835400004
- Scopus ID
- 2-s2.0-85068428802
- Other Identifier
- 991019520543604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology