小肽免疫抑制剂的活性研究  

The Biological Activities of the Small Peptide Immunosuppressant

作　　者：苏丹[1] 孙兆黎[1] 李一[1] 周慧[1] 李惟[1] 

机构地区：[1]吉林大学生命科学院,长春130023

出　　处：《高等学校化学学报》2001年第10期1744-1747,共4页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金 (批准号 :30 0 70 892 )资助

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Con A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 Con A诱导的淋转实验中 ,加入小肽 ( 2 5 0～ 31 .2 5 μg/m L)对淋转反应有明显的抑制作用 ( P 0 .0 1 ) ,在终浓度为 31 .2 5μg/m L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-2 R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 5 d( 1 0 mg/kg)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-S was revealed by DNA sequencing, the peptide Ac XCSSXX NH 2 was synthesized, then purified by HPLC and 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 ConA and IL 2 and the vivo model with liver transplanting of rat. In the LPE induced by ConA, the addition of hexa peptide(250-31 25 μg/mL) had a significant inhibitory effect to LPE( P 0 01). The minimal inhibitory mass concentration is 31 25 μg/mL, with the inhibitory rate of 78.16%. In the LPE induced by IL 2, we obtained the same result as the LPE induced 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.

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 α链 生物活性 白细胞介素2 移植排斥反应 治疗 

分 类 号：R617[医药卫生—外科学] R979.5[医药卫生—临床医学]