New strategy for developing safe foods for celiac patients. Preventing recognition of gluten by tissue transglutaminase through chemical modification of key binding sites

Research Project, 2013 – 2016

Celiac disease is characterized by inflammation of the small intestine associated with intake of gluten proteins. The inflammation starts when gluten in food encounters transglutaminase, an enzyme in the intestinal wall, which deamidates gluten and renders it toxic for genetically predisposed individuals. Aims: To prevent tissue transglutaminase recognition of gluten proteins by chemically modifying binding sites on gluten and to introduce the transglutaminase inhibitor zinc into gluten. We would like to decrease the activity by at least 90%. Methods: We will model gluten with possible inhibitors using a fragment molecular orbital (FMO) approach. The modifications will be produced and in vitro-digested in a computer-operated gastro-intestinal model. Digested, modified and natural gluten will be exposed to a transglutaminase assay to estimate the extent of the deamidation which will be detected by fluorescence measurements. The best candidates will be validated in toxicology studies in human Caco-2 cells and verified to not evoke an immune response in T-cells. Significance: Improvement and increased variation of foods for celiac patients is needed. Gluten-free products are limited and have inferior texture and taste due to the absence of gluten properties. Many natural gluten-free products are contaminated with gluten and are toxic to some celiac patients. The proposed project is an important step to make gluten-containing foods available to celiac patients