Effective Mast Cell Degranulating Peptide Inhibitors of the IgE/FcepsilonRI Receptor Interaction. Export

@article{citeulike:3057755, abstract = {Previous studies with mast cell degranulating (MCD) peptide have shown that peptide [Ala(12)]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 [Ala(12),desLys(21)]MCD 2 and [Ala(12),d-Lys(21)]MCD 4. N-terminus modifications were [desLys(6)-Arg(7)-His(8),Ala(12)]MCD 1, [Ala(6), Ala(12)]MCD 6, and [Val(6),Ala(12)]MCD 7. To assess the role of the Proline(12), analogs [d-Ala(12)]MCD 3 and [Meleu(12)]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 beta-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 beta-hexosaminidase assay, analog [Val(6), Ala(12)]MCD 7 proved to be an excellent inhibitor of IgE-mediated mast cell degranulation.}, address = {Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.}, author = {Buku, Angeliki and Keselman, Inna and Lupyan, Dmitry and Mezei, Mihaly and Price, Joseph A A.}, citeulike-article-id = {3057755}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1747-0285.2008.00684.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18624811}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18624811}, day = {3}, doi = {10.1111/j.1747-0285.2008.00684.x}, issn = {1747-0285}, journal = {Chemical biology \& drug design}, keywords = {ige, ige-receptor, mcd, md, peptide, simulation}, month = {July}, posted-at = {2008-07-29 21:44:13}, priority = {2}, title = {Effective Mast Cell Degranulating Peptide Inhibitors of the IgE/FcepsilonRI Receptor Interaction.}, url = {http://dx.doi.org/10.1111/j.1747-0285.2008.00684.x}, year = {2008} }

TY - JOUR ID - citeulike:3057755 L3 - citeulike-article-id:3057755 N2 - Previous studies with mast cell degranulating (MCD) peptide have shown that peptide [Ala(12)]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 [Ala(12),desLys(21)]MCD 2 and [Ala(12),d-Lys(21)]MCD 4. N-terminus modifications were [desLys(6)-Arg(7)-His(8),Ala(12)]MCD 1, [Ala(6), Ala(12)]MCD 6, and [Val(6),Ala(12)]MCD 7. To assess the role of the Proline(12), analogs [d-Ala(12)]MCD 3 and [Meleu(12)]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 beta-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 beta-hexosaminidase assay, analog [Val(6), Ala(12)]MCD 7 proved to be an excellent inhibitor of IgE-mediated mast cell degranulation. JF - Chemical biology & drug design SN - 1747-0285 AD - Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA. TI - Effective Mast Cell Degranulating Peptide Inhibitors of the IgE/FcepsilonRI Receptor Interaction. KW - ige KW - ige-receptor KW - mcd KW - md KW - peptide KW - simulation AU - Buku, Angeliki AU - Keselman, Inna AU - Lupyan, Dmitry AU - Mezei, Mihaly AU - Price, Joseph A PY - 2008/07/03/ UR - http://dx.doi.org/10.1111/j.1747-0285.2008.00684.x ER -