Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide(534 views) Rossi M, Ruvo M, Marasco D, Colombo M, Cassani G, Verdoliva A
Keywords: Active Cutaneous Anaphylaxis, Allergic Disorders, Passive Cutaneous Anaphylaxis, Antiallergic Agent, Beta N Acetylhexosaminidase, Binding Protein, Immunoglobulin E, Ketotifen, Tg 19320, Tg19318, Unclassified Drug, Animal Cell, Animal Experiment, Animal Model, Article, Atopy, Controlled Study, Drug Dose Increase, Enzyme Linked Immunosorbent Assay, Female, Mast Cell Degranulation, Mouse, Nonhuman, Passive Skin Anaphylaxis, Priority Journal, Protein Analysis, Protein Binding, Protein Determination, Protein Variant, Surface Plasmon Resonance, 4-Dinitrophenol, Anti-Allergic Agents, Biotinylation, Peptides, Protein Conformation, Rattus,
Affiliations: *** IBB - CNR ***
Tecnogen S.p.A., Localita La Fagianeria, 81015 Piana di Monte Verna, CE, Italy
Tecnogen S. p. A., Localita La Fagianeria, 81015 Piana di Monte Verna, CE, Italy
References: Not available.
Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide
Using a combinatorial chemistry approach, we identified a tetrameric tripeptide, denoted Protein A Mimetic (PAM) or TG19318, able to bind to immunoglobulins of different classes and species. The inverso variant, with the tripeptide in the all-D configuration (D-PAM or TG19320) is described as retaining binding properties to Ig. This peptide has now been assayed as a binder for E class immunoglobulins, in linear and competitive ELISA experiments. dot-blot and surface plasmon resonance (SPR) analyses. We show that D-PAM binds IgE with high specificity and selectivity. the interaction being sufficient to inhibit anaphylactic release of beta-hexosaminidase from RBL 2H3 cells, with an IC50 value of 10 mu g/mL. Intradermal administration of D-PAM suppresses PCA in the rat, with an IC50 of 1.25 mu g/kg dose of peptide, while its intraperitoneal injection inhibits mouse PCA with an IC50 of about 7 mg/kg and an efficacy comparable to that of ketotifen. Similarly, D-PAM inhibits ACA in the mouse, with 50% suppression at 10 mg/kg. The results presented here show that the peptide is active on the studied models, with effective doses below toxicity level, hence the molecule is a promising candidate for development of a new class of anti-allergic drugs. (C) 2007 Elsevier Ltd. All rights reserved.
Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide
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Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide