New conformationally restricted analog of the immunosuppressory mini-domain of HLA-DQ and its biological properties.
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.
Szewczuk
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Faculty of Chemistry, University of Wrocław, ul. F. Joliot-Curie 14, 50-383 Wrocław, Poland. szewczuk@wchuwr.chem.uni.wroc.pl
Wilczyński
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Dyba
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M
Petry
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Siemion
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Wieczorek
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D006683:HLA-DQ Antigens / Q000737:chemistry* / Q000276:immunology*; D006967:Hypersensitivity; D051379:Mice; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013154:Spleen / Q000166:cytology; D016305:Thymopentin / Q000737:chemistry; D013997:Time Factors
D000596:Amino Acids; D000939:Epitopes; D006683:HLA-DQ Antigens; D010455:Peptides; D016305:Thymopentin