Structure-activity relationships of a peptide inhibitor of the human FcRn:human IgG interaction.
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Abstract | A family of five peptides was previously discovered by phage display techniques that binds to the human neonatal Fc receptor (FcRn) and inhibits the human IgG:human FcRn protein-protein interaction [Proc. Nat. Acad. Sci. U.S.A.2008, 105, 2337-2342]. The consensus peptide motif consists of the sequence GHFGGXY where X is preferably a hydrophobic amino acid, and also includes a disulfide bridge enclosing 11-amino acids in varying positions about the consensus sequence. We describe herein the structure-activity relationships of one of the five peptides in binding to FcRn using surface plasmon resonance and IgG:FcRn competition ELISA assays. Modifications of the peptide length, cyclization, and the incorporation of amino acid substitutions and dipeptide mimetics were studied. The most potent analogs exhibited a 50- to 100-fold improvement of in vitro activity over that of the phage-identified peptide sequence. |
Year of Publication | 2008
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Journal | Bioorg Med Chem
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Volume | 16
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Issue | 12
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Pages | 6394-405
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Date Published | 2008 Jun 15
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ISSN | 1464-3391
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DOI | 10.1016/j.bmc.2008.05.004
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PubMed ID | 18501614
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