AbstractInitiation 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 (ZnCl₂), and thereby reached a 99% ± 1% inhibition of TG2 activity. In addition, we conducted a pilot experiment in which ascorbyl palmitate was observed to decrease TG2 deamidation of gliadin completely. We propose ascorbyl palmitate in combination with ZnCl₂ with the future perspective to become an additive in celiac-safe foods.