3个六肽的胰岛素受体结合和体内生物活性

为了研究胰岛素受体结合部位的结构和功能，设计并用固相方法合成了３个六肽．在浓度大于１×１０３ｎｍｏｌ／Ｌ时，ｃｙｃｌｏ（Ｐｈｅ－Ｐｈｅ－Ｖａｌ－Ｌｅｕ－Ｔｙｒ－Ｇｌｙ）具有明显的胰岛素受体结合活力；Ｈ－Ｐｈｅ－Ｐｈｅ－Ｖａｌ－Ｌｅｕ－Ｔｙｒ－Ｇｌｙ－ＯＨ的这一活力则不明显；而Ｈ－Ｇｌｙ－Ｇｌｕ－Ａｒｇ－Ｇｌｙ－Ｐｈｅ－Ｐｈｅ－ＯＨ则增强胰岛素和其受体的亲和性．然而，它们都没有体内生物活性．这表明：环六肽部分模拟了胰岛素受体结合部位的空间构象；胰岛素受体结合部位的疏水性和其中的Ｂ２３Ｇｌｙ－Ｂ２４Ｐｈｅ－Ｂ２５Ｐｈｅ对胰岛素和其受体的结合起重要作用．

Insulin Receptor binding and Biological Activities of Three Insulin related Hexapeptides

It is proposed that there exists in insulin a hydrophobic domain related to the binding of insulin with its receptor.In order to study the structure and function of this domain,three hexapeptides were designed and synthesized by the Boc solid phase synthetic strategy.When the concentration was higher than 1×10 3 nmol/L,cyclo(Phe Phe Val Leu Tyr Gly) had a definite capacity of binding to insulin receptor;H Phe Phe Val Leu Tyr Gly OH had very weak such activity;H Gly Glu Arg Gly Phe Phe OH enhanced the affinity of insulin with its receptor.However,all of them showed no in vivo activity.The results suggest that the cyclohexapeptide is to some extent similar to the conformation of the domain concerning the binding of insulin with its receptor.It is concluded that the B 23 Gly B 24 Phe B 25 Phe and the hydrophobility of this domain play an important part in the binding of insulin with its receptor.