【摘要】 为了获得具有与血小板生成素相似的生物学活性且没有其副作用的血小板生成素模拟肽 ,对一种从肽库中筛选到的血小板生成素模拟肽P1进行改构 ,运用多肽化学合成方法制备了模拟肽P2 ,然后进行P2与葡聚糖偶联以及自身氧化形成二聚体 ,利用MTT法测定其体外活性。结果表明 :所获得的血小板生成素模拟肽P2的EC5 0值较P1提高了 70 0倍 ,达到了 2 0nmol/L ,P2与葡聚糖偶联产物D P2以及P2的二聚体形式 (P2 ) 2 的EC5 0值则分别为 0 .35nmol/L和 0 .14nmol/L。将模拟肽给小鼠皮下注射后检测其外周血指标 ,测定结果证实该肽可以显著提高血循环中血小板数量 ,且不影响其他血液学指标。结论 :这种血小板生成素模拟肽在血小板减少性疾病的治疗方面具有潜在的应用前景更多还原

【Abstract】 In order to find a new TPO mimic peptide with similar activity to TPO while reducing the side effects, a TPO mimic peptide(P1) screened from a random peptide library was restructured. The new structure of the TPO mimic peptide(P2) was synthesized. After coupling P2 with Dextran 10 and performing intermolecular oxidation, dextran coupled and dimerized form of P2 were obtained, naming D P2 and (P2) 2 respectively. The activities of the peptides in vitro were measured with MTT method. The results showed that the EC50 of P2 was 20 nmol/L, 700 times higher than P1. The EC50 of D P2 and (P2) 2 were 0.35 nmol/L and0.14 nmol/L, respectively. After administrating to the mouse, the peptides increased the number of platelets in the blood circulation obviously without influence on other blood cells. In couclusion, the TPO mimic peptides have prospects in treating diseases related with thrombocytopenia.更多还原