利用噬菌体肽库筛选TNF-α表位的相关短肽  

Screening for TNF-α related peptides by phage display system

作　　者：叶飞[1] 姜小丹[1] 李卓娅[1] 龚非力[1] 徐勇[1] 冯玮[1] 熊平[1] 

机构地区：[1]华中科技大学同济医学院免疫教研室,武汉430030

出　　处：《中华微生物学和免疫学杂志》2002年第4期366-370,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金资助项目 (批准号:39870 713;392 70 314 )

摘　　要：目的　从噬菌体肽库筛选TNF α相关短肽 ,为临床上治疗肿瘤奠定基础。方法　用可溶性TNF受体Ⅰ (sTNFRⅠ )筛选噬菌体随机 12肽库 ,利用细胞毒效应进行生物学效应筛选 ,再进行单链DNA测序。结果　分别得到若干模拟跨膜型TNF α(TM TNF α)和模拟分泌型TNF α(S TNF α)细胞毒效应的短肽 ,选择细胞毒效应最好的模拟TM TNF α短肽进行人工合成 ,体外实验显示此肽段对S TNF α耐受肿瘤细胞系HL 6 0具有明显细胞毒效应 ,且主要引起靶细胞凋亡。另外 ,利用激光共聚焦显微镜证实该合成肽段不能诱导NF κB发生核转位。结论　获得模拟TM TNF α的短肽 ,为TM TNF α用于临床抗瘤治疗提供新线索。Objective The screen the TNF-α related peptides from phage peptide library for establishing a safe and effective method of antitumor therapy. Methods The soluble TNFRⅠwas used to screen the TNF-α related peptides from phage 12-mer peptide library. The positive phage clones were selected as their cytotoxicity against different target cell lines, then the sequences of single strand DNA were determined. Results TM-TNF-α or S-TNF-α-like peptides were obtained. The most effective peptide mimicking TM-TNF-α was synthesized and able to effectively kill the HL-60 cell line in vitro, that was resistant to S-TNF-α, and induced apoptosis of target cells. In addition, this peptide failed to induce the transposition (from cytoplasma to nuclear) of NF-κB. Conclusion The short peptides mimicking TM-TNF-α, provided a potential therapeutic agent for cancer patients.

关 键 词：噬菌体肽库 跨膜型TNF-Α 模拟短肽 细胞毒效应 细胞凋亡 肿瘤治疗 免疫疗法 肿瘤坏死因子-α 

分 类 号：R392[医药卫生—免疫学]