ИСТИНА

Insufficient and/or improper protein degradation results in the development of various human pathologies. Proteolytic enzymes aimed to improve insufficient proteolytic activity were suggested for the treatment of protease deficiency-induced disorders. Since in some cases human degradome is incapable to support degradation of the entire target protein(s), other organisms can be used as a source of proteases exhibiting additional activities distinct from human enzymes, and plants are perspective candidates for this source. Present study revealed that recombinant cysteine protease Triticain-α from wheat (Triticum aestivum L) refold in vitro into an autocatalytically activated protease possessing glutenase and collagenase activities at acidic or close to neutral pH levels at the temperature of human body. Mass-specrometry analysis of the products of Triticain-α-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 Celiac Disease (CD) patients. Importantly that Triticain-α was found to be relatively stable in the conditions simulating stomach environment. Thus, we are confident that Triticain-α can be used as a basic compound for development of (i) pharmaceuticals for oral administration aimed at release of the active enzyme into the gastric lumen for CD treatment, and (ii) topically active pharmaceuticals for wound debridement applications.