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

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.