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 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.
Rossi
Maria
M
Tecnogen S.p.A., Località La Fagianeria, 81015 Piana di Monte Verna, CE, Italy.
Ruvo
Menotti
M
Marasco
Daniela
D
Colombo
Maurizio
M
Cassani
Giovanni
G
Verdoliva
Antonio
A
D019297:2,4-Dinitrophenol; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D019921:Biotinylation; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D020349:Surface Plasmon Resonance
D018926:Anti-Allergic Agents; D010455:Peptides; D007073:Immunoglobulin E; D006596:Hexosaminidases; D019297:2,4-Dinitrophenol