Blocking IgE with L-glutamic acid analogs as an alternative approach to allergy treatment

Abstract

IgE-mediated allergic diseases have increased in the last decades. The most prevalent allergens from these seeds are Ric c1 and Ric c3, isoforms of 2S albumin. These allergenic proteins cross-react with allergens from peanut, shrimp, fish, corn, gramineous, house dust, and tobacco. The usual allergy treatment employs antihistaminic, immunotherapies and, omalizumab (Xolair)-based anti-IgE therapy. However, antihistaminics relieve symptoms, and the high cost of omalizumab limits its use for continuous treatment. We propose an alternative immunotherapeutic approach, denoted “IgE-blockage” by L-glutamic acid or modified-glutamic acid. Six compounds, D-glutamic acid, L-glutamic acid, N-methyl-L-glutamic acid, N-acetyl-L-glutamic acid, N-(4-nitrobenzoyl)-L-glutamic acid, and N-carbamyl-L-glutamic, were tested as a blocker. To evaluate motor coordination and the sedative/hypnotic activity of L-glutamic acid, a rota-rod test and a thiopental sodium-induced sleeping test were used. The compounds, L-glutamic acid and L-nitrobenzoyl glutamic acid, were the most active compounds to block the interaction of castor allergens with IgE. These compounds also prevent cross-responses with allergens from food sources and inhalants that cross-react with them. In the sleeping test, the groups that received L-glutamic acid at doses of 10 and 30 mg/kg had a sleeping time similar to the vehicle control group. No changes in the animals' behavior were observed and there was no difference between the L-glutamic acid groups and the vehicle control groups in the rota-rod test. L-glutamic acid and L-nitrobenzoyl glutamic acid can used as IgE blocker to prevent allergic diseases.

DOI: http://dx.doi.org/10.5281/zenodo.7686100