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

被引:89
作者
McDonnell, JM
Beavil, AJ
Mackay, GA
Jameson, BA
Korngold, R
Gould, HJ
Sutton, BJ
机构
[1] UNIV LONDON KINGS COLL, RANDALL INST, LONDON WC2B 5RL, ENGLAND
[2] THOMAS JEFFERSON UNIV, JEFFERSON CANC INST, PHILADELPHIA, PA 19147 USA
来源
NATURE STRUCTURAL BIOLOGY | 1996年 / 3卷 / 05期
关键词
D O I
10.1038/nsb0596-419
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have designed synthetic peptide inhibitors of the interaction between 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 second a-chain domain of Fc epsilon RI, 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 IgE binding. The cyclic L- and retro D-peptides exhibited K(D)s of approximately 3 mu M and 11 mu M, respectively, for IgE. Further, the peptides inhibit IgE-mediated mast cell degranulation, an in vitro model of an allergic response.
引用
收藏
页码:419 / 426
页数:8
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