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The Novel BLyS Antagonist-peptibody Inhibits The Interaction Of BLyS With BCMA

Posted on:2014-04-29Degree:MasterType:Thesis
Country:ChinaCandidate:Y TianFull Text:PDF
GTID:2284330422968543Subject:Microbial and Biochemical Pharmacy
Abstract/Summary:PDF Full Text Request
B lymphocyte stimulator (BLyS) antagonists are new therapeutic reagents fortreating the autoimmune diseases. For its roles in autoimmune diseases such assystemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sj grensyndrome (SS), BLyS antagonists have been developed to treat SLE-and RA-likesymptoms in mice and obtained optimistic results. Peptibodies can inhibit thebioactivity of BLyS, the same as other BLyS antagonists: decoyed BLyS receptors andanti-BLyS antibodies. A new optimized BLyS antagonist peptide-BC was designedaccording to our previous work by the computer-aided homology modeling. In thisstudy, to maintain its stability and spatial conformation, the peptide was fused tohuman IgG1Fc to form a peptide-Fc fusion protein–a novel peptibody by geneengineering(BC-Linker-Fc). The ELISA results indicated that the peptibody couldmimic the BCMA well and bind with BLyS in dosage-dependent manner asBCMA-Fc did. This study highlights the possibility of designing BLyS antagonistpeptibody with high biopotency by gene engineering and prokaryotic expression.Thus, these peptibodies bind with BLyS so well that they could be potentialantagonists to treat autoimmune diseases related with BLyS overexpression.
Keywords/Search Tags:autoimmune diseases, B cell maturation antigen (BCMA), Blymphocyte stimulator (BLyS), peptibody, computer-aided homology modeling
PDF Full Text Request
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