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.
Cornell
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Department of Applied Chemistry, Royal Melbourne Institute of Technology, Australia.
Mothes
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D000595:Amino Acid Sequence; D000818:Animals; D002446:Celiac Disease / Q000209:etiology*; D002642:Chick Embryo; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005903:Gliadin / Q000138:chemical synthesis / Q000235:genetics / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D005903:Gliadin