SOLUTION STRUCTURES OF FC-EPSILON-RI ALPHA-CHAIN MIMICS - A BETA-HAIRPIN PEPTIDE AND ITS RETROENANTIOMER

A central event in the development of the allergic response is the int eraction between immunoglobulin E (IgE) and its cellular high-affinity receptor Fc epsilon RI. Allergen-bound IgE mediates the allergic resp onse by binding through its Fc region to its cellular receptor on mast cells and basophils, causing the release of chemical mediators. One s trategy for the treatment of allergic disorders is the use of therapeu tic compounds which would inhibit the interaction between IgE and Fc e psilon RI. Using a structure-based design approach, conformationally c onstrained synthetic peptides were designed to mimic a biologically ac tive beta-hairpin region of the alpha-chain of Fc epsilon RI. Two pept ide mimics of the Fc epsilon RI alpha-chain were previously shown to i nhibit IgE-Fc epsilon RI interactions, one a peptide comprised of L-am ino acids, covalently cyclized by N- and C-terminal cysteine residues, and the other its retroenantiomer. In this paper the solution structu res of these compounds are derived using NMR spectroscopy. The topoche mical relationship between the retroenantiomeric compounds and the str uctural basis of their biological activity is described.