Structure-based design of peptides which inhibit IgE binding to its high affinity receptor FceRI

Abstract

Interaction between immunoglobulin E (lgE) and its high afi:inity receptor. FceRI a-chain, is central in the development of allergic disease. One strategy for the design of therapeutics for the treatment of allergic conditions is the production of compounds which inhibit the interaction between lgl and FceRI. In this study we will describe the structure-t)ased design and development of synthetic peptide inhibitors of the IgE-FceRI a-chain interaction. We have undertaken site-directed mutagenesis of the Fc region of IgI and of FceRI a-chain and have characterized the kinetic and thermodynamic effects of these mutations. On the basis of this work we have mapped "hotspots" of binding energy for..