Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
SetLance srl, via Fiorentina 1, 53100 Siena, Italy.
Molecules. 2014 Jun 3;19(6):7255-68. doi: 10.3390/molecules19067255.
We report the identification of a new human tumor necrosis factor-alpha (TNF-α) specific peptide selected by competitive panning of a phage library. Competitive elution of phages was obtained using the monoclonal antibody adalimumab, which neutralizes pro-inflammatory processes caused by over-production of TNF-α in vivo, and is used to treat severe symptoms of rheumatoid arthritis. The selected peptide was synthesized in monomeric and branched form and analyzed for binding to TNF-α and competition with adalimumab and TNF-α receptors. Results of competition with TNF-α receptors in surface plasmon resonance and melanoma cells expressing both TNF receptors make the peptide a candidate compound for the development of a novel anti-TNF-α drug.
我们报告了一种新的人肿瘤坏死因子-α（TNF-α）特异性肽的鉴定，该肽是通过竞争淘选噬菌体文库筛选出来的。噬菌体的竞争洗脱是使用单克隆抗体阿达木单抗（adalimumab）获得的，阿达木单抗能中和 TNF-α过度产生引起的炎症过程，用于治疗类风湿关节炎的严重症状。所选肽以单体和支链形式合成，并分析其与 TNF-α的结合以及与阿达木单抗和 TNF-α受体的竞争。在表面等离子体共振和表达两种 TNF 受体的黑素瘤细胞中与 TNF-α受体竞争的结果使该肽成为开发新型抗 TNF-α药物的候选化合物。
