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利用体内噬菌体展示技术进行人源肿瘤细胞特异性结合肽的筛选

Selection of the peptides specifically binding to human tumor cells by using phage-display in vivo

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【作者】 绳纪坡; 李赏; 胡宝成;

【Author】 SHENG Ji_Po, LI Shang, HU Bao_Cheng * (Beijing Institute of Biotechnology, Beijing 100071,China)

【机构】 北京生物工程研究所; 北京生物工程研究所 北京100071; 北京100071; 北京100071;

【摘要】 目的 :寻找肿瘤细胞特异性结合肽 ,为肿瘤诊断试剂及肿瘤药物的研制奠定基础。方法 :用培养的人源肿瘤细胞使裸鼠致瘤 ,将随机肽库从裸鼠的尾静脉注射到裸鼠体内 ,循环数分钟后取肿瘤组织及正常对照组织进行噬菌体筛选 ;经过 2~ 3轮体内筛选 ,获得在肿瘤组织中富集的肽段。结果与结论 :利用体内噬菌体展示技术 ,结合人源肿瘤细胞 (SMMC772 1和PLA80 1D)裸鼠致瘤模型 ,从随机十二肽库中成功地筛选到可以较高特异性地结合SMMC772 1肿瘤细胞或肿瘤血管的噬菌体多肽 ,通过对噬菌体单克隆进行测序 ,初步确定了几种可能的多肽基序(motif)。

【Abstract】 Objective:To select the peptides binding to human tumor cells specifically, and to lay a foundation for developing tumor diagnostic agents and antitumor drugs.Methods:Nude mice were inoculated with human tumor cells, then random phagepeptide libraries were injected intravenously (tail vein) into mice.After 2-4 min the mice were sacrificed and the phage rescued from tissues (tumor and control).The phage recovered from the tissues was amplified and reinjected for two consecutive rounds.After selecting for 2-3 rounds in vivo , the phagepeptides that homed to the tumor tissues were obtained.Results and Conclusions: Some phagepeptides which could specifically bind tumor tissues or blood vessels were screened successfully from the random twelvepeptide pool by means of phage display in vivo combined with inoculating humanderived tumor cells (SMMC7721 and PLA801D) to nude mice.After sequencing these positive phages′ ssDNA,several motifs were preliminarily determined.

【基金】 国家自然科学基金资助课题 (3 0 2 714 5 8)
  • 【文献出处】 军事医学科学院院刊 ,Bulletin of The Academy of Military(Medical Sciences) , 编辑部邮箱 ,2003年02期
  • 【分类号】R73-3
  • 【被引频次】4
  • 【下载频次】172
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