Abstract
Recently we described a family of peptides, unrelated in sequence to IgE, that form stable β-hairpins in solution and inhibit IgE activity in the μM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. & Lowman, H. B. (2001)Biochemistry40, 9828–9835]. Using an expanded set of peptide–phage libraries, we found a simpler motif, X2CPX2CYX, for binding to the high-affinity IgE receptor. In solution, one of these peptides spontaneously formed a covalent antiparallel dimer. We subsequently linked these monomers in a single-chain construct on phage and optimized receptor binding. Ultimately, peptides with 30 nM affinity were produced. NMR studies showed that the peptide adopts a stable fold consisting of two “zeta” (ζ)-shaped moieties. Structure–activity analyses reveal a single binding site created by the zeta-dimer, with two tyrosine residues important for structural stability and two proline residues important for FcɛRI binding. The peptides inhibit histamine release from cultured cells and are extremely stable in biological fluids. The zeta peptides appear to act as competitive IgE inhibitors and suggest possibilities for design of novel IgE antagonists.
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Dates
| Type | When |
|---|---|
| Created | 23 years ago (July 26, 2002, 10:36 a.m.) |
| Deposited | 2 years, 4 months ago (April 22, 2023, 8:18 a.m.) |
| Indexed | 1 month, 1 week ago (July 16, 2025, 8:06 a.m.) |
| Issued | 23 years, 6 months ago (Feb. 5, 2002) |
| Published | 23 years, 6 months ago (Feb. 5, 2002) |
| Published Online | 23 years, 6 months ago (Feb. 5, 2002) |
| Published Print | 23 years, 6 months ago (Feb. 5, 2002) |
@article{Nakamura_2002, title={Stable “zeta” peptides that act as potent antagonists of the high-affinity IgE receptor}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.022635599}, DOI={10.1073/pnas.022635599}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Nakamura, Gerald R. and Reynolds, Mark E. and Chen, Yvonne M. and Starovasnik, Melissa A. and Lowman, Henry B.}, year={2002}, month=feb, pages={1303–1308} }