A novel immunosuppressory peptide originating from the ubiquitin sequence.
Ubiquitin is a conservative polypeptide present in every eukaryotic cell. Apart from its involvement in proteasomal degradation and other intracellular signal pathways, it was suggested to play an important role as the extracellular immunomodulator and antimicrobial agent. Moreover, ubiquitin-derived peptides were shown to express significant biological activities. Our previous studies showed a high immunosuppressive potency of the ubiquitin peptic hydrolysate in which we identified over 70 different peptides. The present work focuses on synthesizing the most abundant of these peptides and investigating their immunomodulatory potency. The peptide VKTLTGKTI possessed the highest immunosuppressory activity in AFC experiments, comparable to the previously described LEDGRTLSDY sequence (a previously discovered ubiquitin-derived peptide). Moreover, some of the investigated peptides expressed immunostimulatory effects. These findings support the idea that ubiquitin, together with products of its degradation, could represent a self-regulating immunoregulatory system. Peptide VKTLTGKTI was also tested for its activity to prolong the skin graft survival in mice. The results showed that the investigated peptide significantly extended the skin transplant rejection time, therefore it could be considered as a potential supplementary medicine in the post-transplantation therapy. Moreover, we synthesized two analogs of investigated peptides, first designed to mimic the non-linear epitope consisting of ubiquitin 16-21 and ubiquitin 52-57 fragments, and second designed to mimic the ubiquitin 5-13 hairpin. We also tested their immunosuppressory activity in in vitro experiments.
Faculty of Chemistry, University of Wrocław, Wrocław, Poland.
Paweł
P
Pasikowski
Tomasz
T
Goździewicz
Piotr
P
Stefanowicz
Jolanta
J
Artym
Michał
M
Zimecki
Zbigniew
Z
Szewczuk
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002942:Circular Dichroism; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D006085:Graft Survival; D056724:Immunity, Humoral; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D017433:Protein Structure, Secondary; D016038:Skin Transplantation / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology; D025801:Ubiquitin / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology
D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D025801:Ubiquitin