Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide
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- 作者：Maria Rossi ; Menotti Ruvo ; Daniela Marasco ; Maurizio Colombo ; Giovanni Cassani ; Antonio Verdoliva
- 关键词：IgE ; Allergic disorders ; Passive cutaneous anaphylaxis ; Active cutaneous anaphylaxis
- 刊名：Molecular Immunology
- 出版年：2008
- 出版时间：January 2008
- 年：2008
- 卷：45
- 期：1
- 页码：226-234
- 全文大小：519 K
文摘
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 β-hexosaminidase from RBL 2H3 cells, with an IC50 value of 10 μg/mL. Intradermal administration of D-PAM suppresses PCA in the rat, with an IC50 of 1.25 μg/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.