Effective mast cell degranulating peptide inhibitors of the IgE/FcεRI receptor interaction

Angeliki Buku, Inna Keselman, Dmitry Lupyan, Mihaly Mezei, Joseph A. Price

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Previous studies with mast cell degranulating (MCD) peptide have shown that peptide [Ala12]MCD 8 was an inhibitor of IgE binding to mast cell receptors. In an attempt to produce increased inhibition, analogs were synthesized that maintained the alanine residue in position 12 in the MCD peptide sequence and were further modified at both termini. Analogs modified at the C-terminus were [Ala12,desLys21]MCD 2 and [Ala 12,d-Lys21]MCD 4. N-terminus modifications were [desLys6-Arg7-His8,Ala12]MCD 1, [Ala6, Ala12]MCD 6, and [Val6,Ala 12]MCD 7. To assess the role of the Proline12, analogs [d-Ala12]MCD 3 and [Meleu12]MCD 5 were also synthesized. The analogs were tested for binding to the IgE receptor in cultured mast cells. Inhibitory activity of IgE-caused degranulation was measured using a β-hexosaminidase assay. Circular dichroism (CD) and molecular modeling of selected analogs were used to follow possible structural differences among these analogs. All analogs showed binding affinity to the IgE receptor and inhibition of IgE-induced mast cell degranulation at different levels. Differences in inhibition were most likely because of diverse interactions of the analogs with the receptor as inferred by the CD and modeling studies. Based on the results of the β-hexosaminidase assay, analog [Val6, Ala12]MCD 7 proved to be an excellent inhibitor of IgE-mediated mast cell degranulation.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalChemical Biology and Drug Design
Volume72
Issue number2
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Keywords

  • β-hexosaminidase
  • FcεRI receptor
  • Fluorescence binding
  • IgE
  • MCD peptides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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