6-o-palmitoylascorbic-acid and Celiac-Disease

Initiation of celiac disease is triggered in the gastrointestinal tract by transglutaminase 2 (TG2) assisted deamidation of gluten peptides. Deamidation is a side-reaction to transamidation and occurs if primary amines are absent. In contrast to deamidation, transamidation does not trigger an immune response. The aim of the study was to identify a suitable food additive that interacts with TG2 binding motives in gluten-derived peptides to prevent deamidation/transamidation. Homology modelling of α2-gliadin and computational screening of compounds for their binding affinity to a common TG2 binding motive (P)QLP were done by using computational approaches followed by experimental testing of TG2 activity. A database containing 1174 potential food grade ligands was screened against the model of α2-gliadin (27 out of 33 aa). Out of the five best ligands, ascorbyl palmitate, was observed to decrease TG2 transamidation of gliadin by 82% ± 2%. To completely silence the transamidation, we added zinc chloride (ZnCl

Topics: Ascorbic Acid; Celiac Disease; Chlorides; Drug Evaluation, Preclinical; Epitopes, T-Lymphocyte; Food Additives; Genetic Predisposition to Disease; Gliadin; GTP-Binding Proteins; Humans; Lymphocyte Activation; Models, Molecular; Molecular Docking Simulation; Pilot Projects; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases; Zinc Compounds