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体内筛选展示脑血管内皮选择性定位多肽的噬菌体

In vivo brain blood vessel targeting using phage display peptide libraries

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【作者】 王帅王欣陈红黄秉仁

【Author】 WANG Shuai,WANG Xin,CHEN Hong,HUANG Bing-Ren(Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, National Lab of Medical Molecular Biology, Beijing 100005)

【机构】 中国医学科学院基础医学研究所、中国协和医科大学基础医学院生物化学与分子生物学系医学分子生物学国家重点实验室医学分子生物学国家重点实验室 北京 100005北京 100005北京 100005

【摘要】 目的:通过噬菌体展示技术寻找能够定位于脑部血管内皮的多肽。方法:通过鼠尾静脉注射展示文库,将脑组织中得到的噬菌体体外扩增,重新注人于Balb/c小鼠。如此3轮筛选,测定所获噬菌体的核苷酸顺序及导出展示多肽的氨基酸顺序,并进行免疫组化分析。结果:得到了展示6个多肽序列的噬菌体克隆。展示3个多肽顺序的噬菌体在脑组织中有明显分布,它们是CSKTAEHTC,QLADTTHHRPWP和SWASLPVGMNSW。免疫组化分析显示展示CSKTAEHTC和QLADTTHHRPWP序列的噬菌体在脑部有明显的阳性分布。结论:展示QLADT-THHRPWP的噬菌体可能对脑血管内皮有更好的结合能力。

【Abstract】 Objective : To screen for some specific peptides which can locate in brain blood vessels using phage display pep-tide libraries in vivo. Methods : Peptide display libraries were intravenously injected into Balb/c mice and subsequently rescued the phages from brain; the phages were amplified and reinjected into mice. Three rounds of selection was carried out and the related phage sequences was sequenced. Immunohistochemical analysis was used. Results:Three special peptides of selected 6 phages, each targeted in brain was several-fold more effective than that of the control. They were CSK-TAEHTC, QLADTTHHRPWP, SWASLPVGMNSW. Immunohistochemical analysis showed 2 of 3 peptides obviously stained within the brain capillaries. The 2 peptides were CSKTAEHTC and QLADTTHHRPWP. Conclusion :Two peptides displaying phages can target in the brain blood vessels and the QLADTTHHRPWP is more competent than CSKTAEHTC.

【基金】 国家自然科学基金课题(30070894)
  • 【文献出处】 解剖学杂志 ,Chinese Journal of Anatomy , 编辑部邮箱 ,2003年04期
  • 【分类号】R346
  • 【被引频次】1
  • 【下载频次】65
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