title: Blocking peptides decrease tissue transglutaminase processing of gliadin in vitro.
abstract: Tissue transglutaminase (tTG) plays an important role in celiac disease pathology as it catalyzes deamidation and cross-linking of specific gluten peptides and converts them into potent epitopes recognized by intestinal T-cells. We investigated whether synthetic peptides with high affinity to gliadin could alter tTG activity on gliadin and whole gluten digest. The immobilized substrates were incubated with synthetic peptides identified by the phage display technique and a control peptide with no affinity to gliadin. Transglutaminase activity was measured with time resolved fluorescence. The mean tTG activity, compared to that of the control without the peptides, was reduced by 31, 33, and 36% for three selected gliadin-binding peptides, and 30% for the peptide pool (P < or = 0.001-0.004) when gliadin was the substrate. Finally, substrate specificity experiments suggested that avenin was processed in a manner similar that used for gliadin during in vitro assays with tTG. The results showed that the blocking peptides efficiently reduced tTG processing of gliadin in vitro, and this strategy will be further investigated as an alternative therapy for celiac disease.
authors.affiliation: Department of Chemical and Biological Engineering/Food Science, Chalmers University of Technology, SE-41296 Goteborg, Sweden. karolina.hoffmann@chalmers.se
authors.forename: Karolina
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Marie
authors.initials: M
authors.lastname: Alminger
authors.forename: Thomas
authors.initials: T
authors.lastname: Andlid
authors.forename: Tingsu
authors.initials: T
authors.lastname: Chen
authors.forename: Olof
authors.initials: O
authors.lastname: Olsson
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Sandberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D005903:Gliadin / Q000737:chemistry*; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D005903:Gliadin; D011503:Transglutaminases