title: A novel BLyS antagonist peptide designed based on the 3-D complex structure of BCMA and BLyS.
abstract: B lymphocyte stimulator (BLyS) is a member of tumor necrosis factor (TNF) family. Because of its roles in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome (SS), BLyS antagonists have been tested to treat SLE- and RA-like symptoms in mice and obtained optimistic results. So far, reported BLyS antagonists were mostly decoyed BLyS receptors or anti-BLyS antibodies. In this study, a novel BLyS antagonist peptide, PT, was designed based on the modeling 3-D complex structure of BCMA and BLyS. The interaction mode of PT with BLyS was analyzed theoretically. The results of competitive ELISA demonstrated that PT could inhibit the binding of BCMA-Fc and anti-BLyS antibody to BLyS in vitro. In addition, PT could partly block the proliferating activity of BLyS on mice splenocytes. The BLyS antagonizing activity of PT was significant (p<0.05). This study highlights the possibility of using BLyS antagonist peptide to neutralize BLyS activity. Further optimization of PT with computer-guided molecular design method to enhance its biopotency may be useful in developing new BLyS antagonists to treat BLyS-related autoimmune diseases.
authors.affiliation: Department of Molecular and Cellular Pharmacology, College of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China. jsun@public3.bta.net.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D006801:Humans; D008180:Lupus Erythematosus, Systemic; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012859:Sjogren's Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; C120197:BLyS receptor; D008565:Membrane Proteins; D010455:Peptides; D018124:Receptors, Tumor Necrosis Factor; C439524:TNF protein, human; C505719:TNFSF13B protein, human; C490176:Tnfrsf17 protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha