高等学校化学学报

高等学校化学学报 ›› 2001, Vol. 22 ›› Issue (10): 1744.

• 研究论文 • 上一篇    下一篇

小肽免疫抑制剂的活性研究

苏丹, 孙兆黎, 李一, 周慧, 李惟   

  1. 吉林大学生命科学院, 长春 130023
  • 收稿日期:2000-03-15 出版日期:2001-10-24 发布日期:2001-10-24
  • 通讯作者: 周　慧(1954年出生),女,教授,博士生导师,主要从事生物化学与分子生物学研究.
  • 基金资助:

    国家自然科学基金(批准号:30070892)资助

The Biological Activities of the Small Peptide Immunosuppressant

SU Dan, SUN Zhao-Li, LI Yi, ZHOU Hui, LI Wei   

  1. College of Life Science, Jilin University, Changchun 130023, China
  • Received:2000-03-15 Online:2001-10-24 Published:2001-10-24

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被引次数

3

摘要： 用标准的Fmoc保护氨基酸Nα氨基的固相法合成了6肽Ac-XCSSXX-NH2(—CSS—为保守序列,该设计合成的6肽是从若干单克隆中挑选出与IL-2结合力最高的),经HPLC纯化,并通过MS检测.分别以ConA诱导的淋巴细胞转化实验和IL-2诱导的淋巴母细胞转化实验为体外模型,以大鼠肝脏移植为体内模型,观察小肽对移植排斥的影响.在ConA诱导的淋转实验中,加入小肽(250～31.25μg/mL)对淋转反应有明显的抑制作用(P?0.01),在终浓度为31.25μg/mL时,抑制率达到最高.IL-2诱导的淋转实验得到与上述相符的结果,从而进一步表明:小肽是通过抑制IL-2和IL-2R的结合从而实现其免疫抑制作用的.在大鼠肝脏移植模型中:给术后大鼠注射小肽共5d(10mg/kg)可明显延长进行肝移植后大鼠的存活时间.

关键词: 小肽, 免疫抑制剂, 噬菌体肽库, 器官移植, 白细胞介素-2受体&alpha, 链

Abstract: According to the previous studies, in which we used a monoclonal antibody 5G1 that is specific for the human IL 2 receptor α chain to screen a random hexa peptide library and obtained the phage clone which has good combinative activities studied by Elisa, the consensus sequence motif C-S-Swas revealed by DNAsequencing, the peptide Ac XCSSXX NH2 was synthesized, then purified by HPLCand confirmed by MS. To investigate the biological activities of the hexa peptide, we constructed the vitro model of the lymphocyte proliferation experiment(LPE) induced by ConAand IL 2 and the vivo model with liver transplanting of rat. In the LPEinduced by ConA, the addition of hexa peptide(250-3125 μg/mL) had a significant inhibitory effect to LPE( P-001). The minimal inhibitory mass concentration is 3125 μg/mL, with the inhibitory rate of 78.16%. In the LPEinduced by IL 2, we obtained the same result as the LPEinduced by ConA. So we can say that the peptide realizes its immuno suppresive effect by blocking the combination of IL 2 and IL 2R. In the liver transplanting model of rat, the injection of the peptide to the operated rat in five days would prolong the survival time of the rat.

Key words: Hexa peptide, Immunosuppressant, Phage peptide library, Liver transplant, Interleukin-2 receptor &alpha, chain

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