STRUCTURE-BASED DESIGN AND CHARACTERIZATION OF PEPTIDES THAT INHIBIT IGE BINDING TO ITS HIGH-AFFINITY RECEPTOR

We have designed synthetic peptide inhibitors of the interaction betwe en IgE and its high affinity receptor, Fc epsilon RI. The structure of the second domain of CD2 was used as a modelling template for the sec ond a-chain domain of Fc epsilon RI, the C-C' loop of which has been i mplicated in the interaction with IgE. An L-amino acid peptide and a r etro-enantiomeric D-amino acid peptide were designed to mimic the conf ormation of the C-C' region. Both peptides were cyclized by disulphide bond formation between terminal cysteine residues, and show mirror im age symmetry by circular dichroism analysis. The C-C' peptide mimics a ct as competitive inhibitors of IgE binding. The cyclic L- and retro D -peptides exhibited K(D)s of approximately 3 mu M and 11 mu M, respect ively, for IgE. Further, the peptides inhibit IgE-mediated mast cell d egranulation, an in vitro model of an allergic response.