Structure-activity relationships in coeliac-toxic gliadin peptides.
Computer modelling studies of two groups of biologically-active peptides derived from A-gliadin indicated that the most likely structures were a-helical ones, in the case of serine-containing peptides, and random peptides coil types featuring beta-turns, in the case of proline-rich, tyrosine-containing peptides. The serine-containing group of peptides appear to be essentially cytotoxic in animal models of coeliac disease, whilst the tyrosine-containing group have the capacity to initiate damaging immunological reactions in patients with coeliac disease. Both types of activity in coeliac disease are only possible if there is defective digestion of the active peptides, as mucosal digestion studies indicate. In the case of the serine-containing peptides, activity of the peptides is linked to the presence of PSQQ and also probably QQQP motifs. With the tyrosine-containing peptides, sequences such as QQPY and/or QPYP are associated with immunological activity and hence toxicity.
Cornell
H J
HJ
Department of Applied Chemistry, RMIT University, Melbourne, Victoria, Australia. hugh.cornell@rmit.edu.au
Wills-Johnson
G
G
D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000378:metabolism*; D005903:Gliadin / Q000737:chemistry*; D006860:Hydrogen Bonding; D007413:Intestinal Mucosa / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D010456:Peptides, Cyclic / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D010446:Peptide Fragments; D010456:Peptides, Cyclic; D005903:Gliadin