Design of azidoproline containing gluten peptides to suppress CD4+ T-cell responses associated with celiac disease.
Celiac disease is an intestinal disease caused by intolerance for gluten, a common protein in food. A life-long gluten-free diet is the only available treatment. As it is well established that the interaction between proline-rich gluten derived peptides and the human HLA-DQ2 molecules induces immune responses that lead to disease development, we have now designed a series of gluten peptides in which proline residues were replaced by azidoprolines. These peptides were found to bind to HLA-DQ2 with an affinity similar to that of the natural gluten peptide. Moreover, some of these peptides were found to be non-immunogenic and block gluten induced immune responses. These can thus serve as lead compounds for the development of HLA-DQ2 blocker peptides.
Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
Varsha V
VV
Kapoerchan
Martina
M
Wiesner
Mark
M
Overhand
Gijs A
GA
van der Marel
Frits
F
Koning
Herman S
HS
Overkleeft
D001386:Azides; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002446:Celiac Disease / Q000188:drug therapy* / Q000276:immunology; D015195:Drug Design; D005983:Glutens / Q000737:chemistry* / Q000494:pharmacology*; D006683:HLA-DQ Antigens / Q000187:drug effects; D006801:Humans; D010455:Peptides; D011392:Proline / Q000031:analogs & derivatives*
D001386:Azides; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D010455:Peptides; D005983:Glutens; D011392:Proline