A new FcεRI receptor‐mimetic peptide (PepE) that blocks IgE binding to its high affinity receptor and prevents mediator release from RBL 2H3 cells

Abstract

We have recently reported on a class of IgE-binding peptides designed based on the crystallographic structure of the high affinity FcεRI. Peptides contain receptor key residues located within the two distinct binding sites for IgE and selectively bind IgE with an affinity ranging between 6 and 60 µM. We have here designed and characterized a new molecule containing the receptor loops C'-E and B-C and an optimized linker for joining them made of a Lys side chain and a β-Ala. This new peptide shows an increased affinity (around 30 times) compared to the parent loop C'-E + B-C previously described, while retaining the same two-site mechanism of binding and the same selectivity. It also blocks the binding of IgE to the cell-anchored receptor and efficiently prevents histamine release from mast cells. These properties make the peptide a useful scaffold for the development of new anti-allergic drugs.