title: An optimized B lymphocyte stimulator (BLyS) antagonist peptide inhibits the interaction of BLyS with BCMA.
abstract: B lymphocyte stimulator (BLyS) antagonists are new therapeutic reagents for treating the autoimmune diseases. Peptibodies can inhibit the bioactivity of BLyS, the same as other BLyS antagonists: decoyed BLyS receptors and anti-BLyS antibodies. In this study, a new optimized BLyS antagonist peptide was designed according to our previous work by the computer-aided homology modeling. Competitive ELISA showed that the peptide at 100 μg/ml could inhibit 54 % of the BCMA-Fc binding to BLyS. To maintain its stability and spatial conformation, the peptide was fused to human IgG1 Fc to form a peptide-Fc fusion protein-a novel peptibody by gene engineering. ELISA indicated that the peptibody could bind with BLyS in dosage-dependent manner as BCMA-Fc did. This study highlights the possibility of designing and optimizing BLyS antagonist peptides with high biopotency by the computer-aided design. Thus, these peptides could neutralize BLyS activity and be potential antagonists to treat autoimmune diseases related with BLyS overexpression.
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Zhu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Bei-Fen
authors.initials: BF
authors.lastname: Shen
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
mesh_terms: D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D053301:B-Cell Maturation Antigen / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007155:Immunologic Factors; D010455:Peptides; D011993:Recombinant Fusion Proteins; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human