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

Abstract

P.E.D. synthesized and characterized all compounds used in this study, performed most in vitro experiments, and analyzed these data, made all figures, and wrote the manuscript. B.B. and P.E.D. conceived of the idea for the study, designed the molecules, and designed all experiments. T.K. helped in experimental design and manuscript writing and editing. B. Kim performed affinity measurements for cHBI compounds and aided with in vitro studies. B. Koh and A.A.Q. performed all in vivo murine experiments and performed analysis. M.H.K. designed in vivo experiments, analyzed in vivo data, and helped to edit the manuscript.

Nanoarchitectures for efficient IgE cross‐linking on effector cells to study amoxicillin allergy

“…13 Spontaneous conjugation of AX occurs due to the structural propensity of its βlactam ring opening by the nucleophilic primary amines from proteins that results in the amoxicilloyl (AXO) antigenic determinant. 14 The immunological recognition of such multivalently presented antigenic determinants on a conjugate by, at least, two adjacent IgE antibodies that are bound to their high-affinity receptor (FcεRI) on the surface of tissue mast cells (MCs) or circulating basophils, results in an intricate process of IgE cross-linking, [15][16][17][18] releasing preformed inflammatory mediators and eliciting the acute allergic response. 15,19 The efficiency of the stimulation on cell degranulation is dependent on many factors, including the drug antigenic determinant structure, 18,20 its valency on the conjugate or complete antigen, 21,22 the size of the conjugate, 15,23 the proximity of the IgE epitopes, 24 and the steric hindrance.…”