ИСТИНА

The term gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten proteins are highly resistant to hydrolysis mediated by proteases of human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. If nowadays gluten-free diet (GFD) is applied broadly for CD treatment, such a diet may be unsuitable for NCGS treatment because in this case gluten not always arises as the major or exclusive culprit of gastrointestinal disorder. Furthermore, it is some physicians’ opinion that GFD can be deficient in fiber as well as in other vitamins and minerals. In this regard development of alternative medicinal approaches to GFD for effective gluten intolerance treatment is extremely important. Since human digestive systems are incapable of degrading the entire gluten proteins, other organisms can be used as a source of proteases exhibiting additional activities helping an organism in complete gluten degradation, and plants are perspective candidates for this source. In this study recombinant wheat cysteine protease Triticain- was shown to possess glutenase activity at acidic (or close to neutral) pH levels at the temperature of human body. Further analysis showed that the products of Triticain--catalyzed gluten hydrolysis revealed multiple cleavage sites within the sequences of gliadin toxic peptides, in particular, in the major toxic 33-mer α-gliadin-derived peptide initiating inflammatory responses to gluten in CD patients. Triticain- was found to be relatively stable in the conditions simulating stomach environment. We conclude that Triticain- can be exploited as a basic compound for development of pharmaceuticals for oral administration aimed at release of the active enzyme into the gastric lumen for CD treatment.