Using Chemical Shift Perturbations to Validate and Refine the Docking of Novel IgE Antagonists to the High-Affinity IgE Receptor

The binding of IgE to its high-affinity receptor, FcεRI, is fundamental to allergic disease. Molecules that block this interaction could therefore act as useful therapeutics for the treatment of asthma, allergic rhinitis, and other forms of atopy. To this end, binding selections using the extracellular portion of the α-chain of FcεRI (FcεRIα) and polyvalent peptide-phage libraries have yielded two distinct classes of peptide ligands that antagonize IgE binding to its receptor and prevent downstream IgE-mediated signaling events in basophils [1,2]. NMR spectroscopy has been used to characterize the structures of these peptide antagonists and their modes of binding to FcεRIα.