Characterization of the gliadin-derived peptides which are biologically active in coeliac disease.
Reversed-phase HPLC on C18 silica gel at pH 3.5 was used to separate peptides in fraction 9, a mixture of peptides of unknown composition obtained from an enzymic digest of wheat gliadin. This fraction, which has been shown to be toxic to individuals with coeliac disease, yielded a principal peak as well as many minor peaks after HPLC. The significant peaks were subjected to amino acid analysis. The principal peak obtained was purified by rechromatography at pH 6.0 and shown to contain a dodecapeptide of sequence H-Arg-Pro-Gln-Gln-Pro-Tyr-Pro-Gln-Pro-Gln-Pro-Gln-OH. This peptide may have been derived from regions in the A-gliadin molecule corresponding to amino acids numbered 75-86 or from homologous regions in other gliadin molecules. Preliminary results indicate that it is active in two in vitro models of coeliac disease and that it could be the source of one of the undigested peptides (Hexapeptide II, (Glx)3, (Pro)2, Tyr) obtained from coeliac mucosal digestion of fraction 9. Some active serine-containing peptides were also obtained from chromatography at pH 3.5 and attempts are being made to correlate these with the other undigested peptide (Hexapeptide I) of composition (Glx)3, (Pro)2, Ser, obtained after coeliac mucosal digestion of fraction 9.
Cornell
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Department of Applied Chemistry, Royal Melbourne Institute of Technology, Australia.
Wieser
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Belitz
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002446:Celiac Disease / Q000139:chemically induced*; D002851:Chromatography, High Pressure Liquid; D005903:Gliadin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
D000596:Amino Acids; D010446:Peptide Fragments; D005903:Gliadin