A Novel Family of Hairpin Peptides That Inhibit IgE Activity by Binding to the High-Affinity IgE Receptor
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- 作者：Gerald R. Nakamura ; Melissa A. Starovasnik ; Mark E. Reynolds ; and Henry B. Lowman
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：August 21, 2001
- 年：2001
- 卷：40
- 期：33
- 页码：9828 - 9835
- 全文大小：203K
- 年卷期：v.40,no.33(August 21, 2001)
- ISSN：1520-4995
文摘
A family of structured peptides that bind to Fc
RI
, the -chain of the high-affinity receptorfor IgE, has been identified. Binding selections using FcRI and polyvalent peptide-phage libraries yieldeda dominant 18-residue peptide-phage clone, as well as related sequences that did not resemble fragmentsof IgE. Synthetic peptides based on these sequences inhibited IgE binding to its receptor, and were foundby NMR analysis to adopt a stable 
-hairpin structure in solution. Optimized peptides with micromolarreceptor affinity exhibited high stability in biological fluids and inhibited cellular histamine release in anin vitro bioassay of IgE activity. The structure-activity relationships of these peptides, which are lessthan 1% of the size of IgE, suggest an overlap between their binding site and that of IgE on FcRI. Thus,the peptides demonstrate that blocking a small epitope on this receptor chain is sufficient to block IgEactivity. Such structured peptides represent a possible starting point for the design of novel antagonists,and offer the potential for testing in vivo a new approach for treating allergic disease.
RI, the -chain of the high-affinity receptorfor IgE, has been identified. Binding selections using FcRI and polyvalent peptide-phage libraries yieldeda dominant 18-residue peptide-phage clone, as well as related sequences that did not resemble fragmentsof IgE. Synthetic peptides based on these sequences inhibited IgE binding to its receptor, and were foundby NMR analysis to adopt a stable -hairpin structure in solution. Optimized peptides with micromolarreceptor affinity exhibited high stability in biological fluids and inhibited cellular histamine release in anin vitro bioassay of IgE activity. The structure-activity relationships of these peptides, which are lessthan 1% of the size of IgE, suggest an overlap between their binding site and that of IgE on FcRI. Thus,the peptides demonstrate that blocking a small epitope on this receptor chain is sufficient to block IgEactivity. Such structured peptides represent a possible starting point for the design of novel antagonists,and offer the potential for testing in vivo a new approach for treating allergic disease.