38. A-GLIADIN RELATED SYNTHETIC PEPTIDES AGGLUTINATE UNDIFFERENTIATED K TO 562 S CELLS AND AFFECT IN VITRO DEVELOPING FETAL RAT INTESTINE AND ULTURED ATROPHIC COELIAC MUCOSA

Abstract

Peptides from wheat gliadins, A-gliadin and prolamins from cereals toxic for coeliac patients agglutinate K 562(5) cells; they also damage in vitro cultured fetal rat intestine and atrophic coeliac mucosa. The largest common sequences among the in vitro active A-gliadin peptides were -Pro-Ser-Gln-Gln and -(Gln)3-Pro-. The following peptides all containing the aminoacid sequence -(Gln)3-Pro have been synthesized: the pentapeptide Tyr-(Gln)3-Pro, its dimer and tetramer and the epta-peptide Gln-Pro-Tyr-(Gln)3-Pro in their free and N-acetylated forms and the Pyro-glutamic derivate of the heptapeptide (Pyr 7). Pyr 7 agglutinated cells and inhibited the in vitro development of fetal rat intestine (medium's concentration 0.5-2 mg/ml); it was non toxic on the in vitro cultured coeliac atrophic mucosa. The N-acetylated form of the pentapeptide's tetramer (1 mg/ml) also damaged the atrophic coeliac mucosa in 3 cultured biopsies. These results suggest that the sequence -(Gln)3-Pro when part of a larger peptide may be toxic in vitro for the atrophic coeliac mucosa.