title: [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors.
abstract: An effort was made to discover mast cell degranulating (MCD) peptide analogs that bind with high affinity to mast cell receptors without triggering secretion of histamine or other mediators of the allergic reaction initiated by immunoglobulin E (IgE) after mast cell activation. Such compounds could serve as inhibitors of IgE binding to mast cell receptors. An alanine scan of MCD peptide reported previously showed that the analog [Ala12]MCD was 120-fold less potent in histamine-releasing activity and fivefold more potent in binding affinity to mast cell receptors than the parent MCD peptide. Because this analog showed marginal intrinsic activity and good binding affinity it was subsequently tested in the present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed a 50% inhibition of IgE binding to the Fc epsilon RI alpha mast cell receptor by using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization. Furthermore, in a beta-hexosaminidase secretory assay, the peptide also showed a 50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made to relate structural changes and biologic differences between the [Ala12]MCD analog and the parent MCD peptide. The present results show that [Ala12]MCD may provide a base for designing agents to prevent IgE/Fc epsilon RI alpha interactions and, consequently, allergic conditions.
authors.affiliation: Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029, USA. angeliki.buku@mssm.edu
authors.forename: A
authors.initials: A
authors.lastname: Buku
authors.forename: B A
authors.initials: BA
authors.lastname: Condie
authors.forename: J A
authors.initials: JA
authors.lastname: Price
authors.forename: M
authors.initials: M
authors.lastname: Mezei
mesh_terms: D000409:Alanine / Q000737:chemistry*; D019943:Amino Acid Substitution; D000818:Animals; D007073:Immunoglobulin E / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008958:Models, Molecular; D009010:Monte Carlo Method; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis
chemical_list: D010455:Peptides; D011956:Receptors, Cell Surface; C008331:mast cell degranulating peptide; D007073:Immunoglobulin E; D001619:beta-N-Acetylhexosaminidases; D000409:Alanine