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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
In order to obtain the thrombopoietin mimetic peptide with similar biological activity to thrombopoietin without any side effect, a novel peptide, thrombopoietin mimic peptide P1, was screened from the peptide library and prepared by peptide chemical synthesis Peptide P2 was mimicked, and then P2 was coupled with dextran and self-oxidized to form dimer, and its in vitro activity was measured by MTT assay. The results showed that the obtained EC50 value of the thrombopoietin mimic peptide P2 was 70 0 times higher than that of P1, reaching 20 nmol / L. The P2 and glucan conjugate product D P2 and the dimer form of P2 (P2 ) 2 EC50 values were 0.35nmol / L and 0.14nmol / L. The simulated peptide was subcutaneously injected into mice to test its peripheral blood indexes. The results confirmed that the peptide can significantly increase the number of platelets in the blood circulation without affecting other hematological indexes. Conclusion: This thrombopoietin mimetic peptide has potential applications in the treatment of thrombocytopenic diseases