Synthetic peptides with high affinity to gliadin reduce tissue transglutaminase activity on gliadin in vitro

Tissue transglutaminase (tTG) plays an important role in celiac disease development as it generates epitopes from gluten peptides that trigger the immune response that results in the intestinal inflammation (1). We investigated if tTG‐catalyzed modification of gliadin could be reduced in vitro by synthetic peptides selected for high affinity to gliadin. Gliadin‐binding peptides were selected with phage display. Three blocking peptides P61, P64, and P22, a peptide pool, and a control peptide PC31, were used in the tTG activity assay (2). Western blot analysis of gliadin‐blocking peptide complexes was performed to confirm the binding and characterize gliadin regions preferred by blocking peptides. Blocking peptides significantly reduced the enzymatic processing of gliadin by tTG by ~36% for P22, ~33% for P64, ~31.4% for P61, and ~30% for the peptide pool as compared to the controls (3). Western blot revealed that peptides P61 and P64 interacted with a broad spectrum of gliadin sequences, and wheat allergens α‐amylase/trypsin inhibitors in vitro . Blocking peptides have a potential for gluten detoxification and could after further research be evaluated as additives in designing food products with low gluten amount. Founding Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning no: 222‐2004‐2705.