采用双杂交技术以受体为靶标的药物筛选体系的研究

Several analysis models for the study of interaction between peptide ligand and receptor and the drug screening were developed based on the yeast two hybridization and phage display technology. Peptides that can bind to TNFa and TNF receptor were selected from phage displayed 12mer peptide libraries, Moreover, these peptides, when displayed on the surface of phage, can inhibit the cytotoxicity of TNFa. The similar results were obtained when synthesized peptide or recombinant fusion peptide were used in the biological activity assay, indicating their potential application as anti-TNF drug. The peptides we have screened have significant structural identity, which providing further information for rational design of anti-TNF drugs. The current study also exploited a route for the screening of small molecular drugs.

酵母双杂交作为近年来出现的研究蛋白相互作用的体内遗传体系，可能在药物筛选领域发挥独特作用。本研究拟以肿瘤坏死因子α（TNFα）及其受体相互作用为模型，通过双杂交系成秆∮隩NF受体具有不同亲和力的TNFα突变体，从而探讨酵母双杂交作为新型药物筛选体档目尚行裕饨兄凭哂薪系投靖弊饔玫腡NFα制品并用于肿瘤的临床治疗奠定基础。