Further studies of the in vitro activity of synthetic gliadin peptides in coeliac disease

Abstract

Studies of in vitro activity of synthetic peptides derived from the A-gliadin structure were carried out using assays based on cultures of foetal chick intestinal mucosa and on incubation with rat liver lysosomes. The peptide corresponding to residues 11–19, displayed very high activity in the chick intestinal assay, but was only weakly active in the lysosomal assay. Peptide 9–19 was highly active in the chick intestinal assay but was only mildly active in the lysosomal assay. Peptide 8–19 was still appreciably active in both assays. The results on this group of peptides suggest the importance of residues 8–12 to activity and possibly also of a N-terminal glutamine residue. The peptide 213–227, found in a sub-fraction of fraction 9, was only weakly active in both assays, indicating that the PSQQ motif was not solely responsible for toxicity. Thus, as the peptide 208–219 was shown previously to be active in the chick intestinal assay, it is likely that the 208–212 region of this peptide is of prime importance in conferring activity. The results show, for the first time, that a nonapeptide from the N-terminal region of A-gliadin is very active in an in vitro model of toxicity in coeliac disease.