title: Towards Celiac-safe foods: Decreasing the affinity of transglutaminase 2 for gliadin by addition of ascorbyl palmitate and ZnCl2as detoxifiers.
abstract: 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 (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 ZnCl2with the future perspective to become an additive in celiac-safe foods.
authors.affiliation: Chalmers University of Technology, Department of Biology and Biological Engineering, The division of Food and Nutrition Science, 412 96, Gothenburg, Sweden.
authors.forename: N
authors.identifier: 0000-0003-2399-985X
authors.initials: N
authors.lastname: Engstrom
authors.affiliation: University of Gothenburg, Department of Chemistry and Molecular Biology, 405 30, Gothenburg, Sweden.|UdelaR, Facultad de Química, Computational Chemistry and Biology Group, 11800, Montevideo, Uruguay.
authors.forename: P
authors.initials: P
authors.lastname: Saenz-Méndez
authors.affiliation: Chalmers University of Technology, Department of Physics, 412 96, Gothenburg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Scheers
authors.affiliation: Chalmers University of Technology, Department of Biology and Biological Engineering, The division of Food and Nutrition Science, 412 96, Gothenburg, Sweden. nathalie.scheers@chalmers.se.
authors.forename: N
authors.initials: N
authors.lastname: Scheers
mesh_terms: D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002446:Celiac Disease / Q000201:enzymology / Q000276:immunology*; D002712:Chlorides / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005503:Food Additives / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005903:Gliadin / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010865:Pilot Projects; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D018984:Epitopes, T-Lymphocyte; D005503:Food Additives; D017967:Zinc Compounds; C016837:zinc chloride; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid