New conformationally restricted analog of the immunosuppressory mini-domain of HLA-DQ and its biological properties |
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Authors: | Szewczuk Z Wilczyński A Dyba M Petry I Siemion I Z Wieczorek Z |
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Institution: | Faculty of Chemistry, University of Wroc?aw, ul. F. Joliot-Curie 14, 50-383 Wroc?aw, Poland. szewczuk@wchuwr.chem.uni.wroc.pl |
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Abstract: | Our previous studies revealed that the nonapeptide fragment of HLA-DQ located in the beta 164-172 loop of the Thr-Pro-Gln-Arg-Gly-Asp-Val-Tyr-Thr sequence suppresses the immune humoral and cellular responses 30]. Based on the crystal structure of HLA-class II molecules we designed and synthesized a cyclic analog with restricted conformation, cyclo(Suc-Thr-Pro-Gln-Arg-Gly-Asp-Val-Lys)-Thr-OH (Suc = succinyl) by reacting a Lys side chain with a succinylated N-terminus. The cyclization product more potently suppresses the cellular immune response than its linear counterparts and is efficiently cleaved by trypsin. The results indicate that the beta 164-172 loop may serve as a functional epitope on the HLA class II surface for intermolecular binding. |
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Keywords: | Histocompatibility antigen Thymopentin analogs Immunosuppressors RGD sequence Cyclic peptide analog Proteolytic stability |
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