Towards Celiac-safe foods: Decreasing the affinity of transglutaminase 2 for gliadin by addition of ascorbyl palmitate and ZnCl
| Autor: | N, Engstrom, P, Saenz-Méndez, J, Scheers, N, Scheers |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Transglutaminases Drug Evaluation Preclinical nutritional and metabolic diseases Epitopes T-Lymphocyte Pilot Projects Ascorbic Acid Lymphocyte Activation digestive system diseases Gliadin Article Molecular Docking Simulation Celiac Disease Chlorides GTP-Binding Proteins Zinc Compounds Humans Food Additives Genetic Predisposition to Disease Protein Glutamine gamma Glutamyltransferase 2 |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 ZnCl2 with the future perspective to become an additive in celiac-safe foods. |
| Databáze: | OpenAIRE |
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