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目的 从噬菌体随机多肽库中筛选出与肿瘤坏死因子 α(TNF α)特异结合 ,并能阻断其生物活性的小肽 ,为建立一种新型的抗TNF α多肽药物奠定基础。方法 用突变体TNF α和天然型TNF α分别作为靶蛋白 ,用噬菌体随机多肽库进行多次淘筛 ,经序列测定及体外酶联免疫吸附法(ELISA)实验选出候选多肽 ,进行抗TNF α诱导的L92 9细胞毒作用。结果 筛选到的二个序列不同但有一定相关性的候选小肽 ,其中由天然型TNF α作为靶蛋白筛选出的 12肽具有抗TNF α诱导的L92 9细胞毒作用。结论 这些序列可以做为合成小肽TNF α活性拮抗剂的依据
OBJECTIVE: To screen out a small peptide that binds to tumor necrosis factor α (TNFα) specifically and block its biological activity from phage random peptide library, which will lay the foundation for the establishment of a new anti-TNF α peptide drug. Methods Mutant TNFα and native TNFα were used as target proteins, respectively, and screened by phage random peptide library for several times. Candidate polypeptides were selected by sequence analysis and enzyme-linked immunosorbent assay (ELISA) Induced L92 9 cytotoxicity. As a result, two candidate small peptides with different sequences but some correlations were screened. Among them, the 12 peptides screened by native TNFα as the target protein had anti-TNFα-induced L92 9 cytotoxicity. Conclusion These sequences can be used as the basis for the synthesis of small peptide TNFα antagonists