艾塞那肽的合成

Synthesis of Exenatide

艾塞那肽是胰高血糖素样肽-1(GLP-1)的类似物,由39个氨基酸组成,具有双激素靶向调控血糖的作用。该文对艾塞那肽的合成方法进行了研究,将原肽拆分成6个全保护片段,分别经过独立的固相或液相方法合成,然后对片段进行组装,经切割、纯化,得到艾塞那肽产品0.98 g,纯度﹥98%,总收率33.8%。切割时保留Fmoc-保护基可以使目标峰与杂峰有效分离。该方法结合了固相和液相合成的特点,与传统方法相比,是一种周期较短、纯化方便和收率较高的合成艾塞那肽的方法。

Exenatide, an analogue of glu residues and adjusts blood glucose level cagon-like peptide 1 （ GLP - 1 ）, consists of 39 amino-acid through bidirectional hormone-targeted regulation. However, there are still many challenges about its synthetic methods. Herein, we split Exenatide into six fully protected peptide fragments and each fragment was synthesized by the solid-phase or liquid-phase method,respectively. After two-step cleavages and purifications, the final product of 0. 98 g （yield： 33.8% ,purity 〉 98% ） was obtained. The Fmoc-protective group attached to the Exenatide after the first step cleavage can enhance the separation of target from impurity efficiently in the purification step. The results show that this method, with the advantages of both solid-phase and liquid-phase syntheses, is a short-cycled, more convenient method and the yield is higher.