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Structure based design and characterization of peptides that inhibit IgE binding to its high-affinity receptor

Nature Structural Biology volume 3, pages 419–426 (1996)Cite this article

Abstract

We have designed synthetic peptide inhibitors of the interaction between IgE and its high affinity receptor, FcεRI. The structure of the second domain of CD2 was used as a modelling template for the second α-chain domain of FcεRI, the C-C′ loop of which has been implicated in the interaction with IgE. An L-amino acid peptide and a retro-enantiomeric D-amino acid peptide were designed to mimic the conformation of the C-C′ region. Both peptides were cyclized by disulphide bond formation between terminal cysteine residues, and show mirror image symmetry by circular dichroism analysis. The C-C′ peptide mimics act as competitive inhibitors of lgE binding. The cyclic L- and retro D-peptides exhibited KDs of approximately 3 μM and 11 μM, respectively, for IgE. Further, the peptides inhibit IgE-mediated mast cell degranulation, an in vitro model of an allergic response.

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Authors and Affiliations

  1. The Randall Institute, King's College London, 26–29 Drury Lane, London, WC2B 5RL, UK

    J.M. McDonnell, A.J. Beavil, G.A. Mackay, H.J. Gould & B.J. Sutton

  2. The Jefferson Cancer Institute, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania, 19147, USA

    B.A. Jameson & R. Korngold

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  1. J.M. McDonnell
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  2. A.J. Beavil
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  7. B.J. Sutton
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McDonnell, J., Beavil, A., Mackay, G. et al. Structure based design and characterization of peptides that inhibit IgE binding to its high-affinity receptor. Nat Struct Mol Biol 3, 419–426 (1996). https://doi.org/10.1038/nsb0596-419

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