Design of azidoproline containing gluten peptides to suppress CD4+ T-cell responses associated with celiac disease |
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Authors: | Kapoerchan Varsha V Wiesner Martina Overhand Mark van der Marel Gijs A Koning Frits Overkleeft Herman S |
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Institution: | Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2300 RA, Leiden, The Netherlands. |
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Abstract: | 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. |
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