Biotinylated Heptapeptides Containing D-amino Acids as Potential Anti-allergic Agents Targeting Cysteinyl Leukotrienes

Cysteinyl leukotrienes (cysLTs) are secreted by mast cells and represent key lipid mediators in allergic airway inflammation. We recently reported that biotinylated heptapeptides containing D-amino acids suppress mast cell degranulation and exhibit pronounced anti-allergic effects. In this study, we aimed to investigate the effects of these peptides on the production of cysLTs by immunoglobulin E (IgE)/antigen-activated mast cells, as well as on in vivo allergic airway inflammation. CysLT release from IgE/antigen-activated RBL-2H3 cells was quantified using an enzyme-linked immunosorbent assay. The effects of biotinylated peptides on ovalbumin-induced allergic airway inflammation were assessed using bronchoalveolar lavage fluid (BALF) analysis. The effects of biotinylated peptides on the bioactivity of leukotriene C₄ (LTC4) were evaluated using a mouse hind paw edema model. Among the biotinylated peptides, Peptide 2 (D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp) markedly inhibited cysLT release from RBL-2H3 cells and LTC4-induced paw edema in mice. The intranasal administration of high-dose (30–100 nmol/mouse) Peptide 2 caused significantly larger reduction in the counts of total inflammatory cells, lymphocytes, and eosinophils in BALF than did low-dose (0–10 nmol/mouse) Peptide 2. The systemic administration of Peptide 2 had slight effects at all doses. Peptide 2 is a promising candidate as a novel anti-allergic agent targeting IgE/antigen-activated mast cell-derived cysLTs for the treatment of allergic diseases.