Abstract 2428 Celiac Disease: TG2 To Get A Clue

Celiac's Disease (CD) is an autoinflammatory disease resulting in damage to the small intestine and is caused when the transferrin receptor CD71, binds to and moves the gliadin peptide of gluten into the lamina propria. Type 2 transglutaminase (TG2) modifies the gliadin peptide, particularly peptide 31-43 of the α-gliadin (P31-43), deamidating it and producing negatively charged glutamic acid from gliadin P31-43. This causes previously restricted DQ2 Human Leukocyte Antigen haplotype (HLA-DQ2) heterodimers to trigger an immune response, causing inflammation and tissue damage to the small intestine.Transglutaminase 2 inhibitor (TAK-227/ZED1227), is an oral capsule drug targeted for the duodenum region of the intestines. The drug blocks TG2 at the catalytic center, specifically targeting tryptophan-241 (trp-241), which is an essential aspect of the catalytic activity that takes place in the center of TG2, as it reacts with the misplaced gliadin. This inhibits the deamidation of gliadin P31-43 that would cause the reaction in the catalytic nucleic center of TG2, and prevents the gluten-induced T-cell activation, as well as the formation and buildup of deamidated gluten. Our research, in collaboration with the Center of BioMolecular Modeling at 3D Molecular Designs, proposes that the relationship between the inhibitory effects of TAK-227/ZED1227 on TG2's deamidation of the gliadin P31-43 is further tested in correlation with other tryptophan chains located in or near the catalytic nucleic center of TG2, such as trp-332, to negate or correlate the adverse effects TAK-227/ZED1227, and increase its effectiveness, in treating Celiac Disease.