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.