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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

IgE Receptors
Mast Cells
Immunoglobulin E
Hexosaminidases
Assays
Molecular modeling
Alanine
Cell Degranulation
Circular Dichroism
mast cell degranulating peptide
Cultured Cells

Keywords

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

Cite this

Buku, Angeliki ; Keselman, Inna ; Lupyan, Dmitry ; Mezei, Mihaly ; Price, Joseph. / Effective mast cell degranulating peptide inhibitors of the IgE/FcεRI receptor interaction. In: Chemical Biology and Drug Design. 2008 ; Vol. 72, No. 2. pp. 133-139.
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Effective mast cell degranulating peptide inhibitors of the IgE/FcεRI receptor interaction. / Buku, Angeliki; Keselman, Inna; Lupyan, Dmitry; Mezei, Mihaly; Price, Joseph.

In: Chemical Biology and Drug Design, Vol. 72, No. 2, 01.08.2008, p. 133-139.

Research output: Contribution to journalArticle

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