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.
Biotechnol Lett. 2013 Apr;35(4):523-8. doi: 10.1007/s10529-012-1117-y. Epub 2012 Dec 15.
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.
B 淋巴细胞刺激因子 (BLyS) 拮抗剂是治疗自身免疫性疾病的新型治疗试剂。肽抗体可以抑制 BLyS 的生物活性，与其他 BLyS 拮抗剂（诱饵 BLyS 受体和抗 BLyS 抗体）相同。在这项研究中，根据我们之前的工作，通过计算机辅助同源建模设计了一种新的优化 BLyS 拮抗剂肽。竞争性 ELISA 表明，肽在 100μg/ml 时可以抑制 54%的 BCMA-Fc 与 BLyS 的结合。为了保持其稳定性和空间构象，该肽与人 IgG1 Fc 融合形成一种新型的肽-Fc 融合蛋白——肽抗体。ELISA 表明，肽抗体可以像 BCMA-Fc 一样与 BLyS 呈剂量依赖性结合。这项研究强调了通过计算机辅助设计设计和优化具有高生物活性的 BLyS 拮抗剂肽的可能性。因此，这些肽可以中和 BLyS 的活性，成为治疗与 BLyS 过表达相关的自身免疫性疾病的潜在拮抗剂。
