Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide.

Abstract:

: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 microg/mL. Intradermal administration of D-PAM suppresses PCA in the rat, with an IC50 of 1.25 microg/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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Rossi M,Ruvo M,Marasco D,Colombo M,Cassani G,Verdoliva A

doi

10.1016/j.molimm.2007.04.020

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

226-34

issue

1

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(07)00168-X

journal_volume

45

pub_type

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