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Exendin-4是首个获准上市的肠促胰素类似物药物,可模拟人体自身激素GLP-1的功能,不仅改善血糖,还能促进胰岛β细胞新生、增殖,抑制β细胞凋亡,改善β细胞功能,促进胰岛素分泌,增加机体对胰岛素的敏感性。根据Exendin-4的潜在市场价值,以Fmoc固相合成策略为基础,NMP为反应溶剂,以HOBt/DIC为缩合剂,添加盖帽程序,优化合成工艺条件。肽树脂裂解采用TFA/Phenol/TIS裂解液,并应用高效液相色谱和四级杆-飞行时间串联质谱对其进行分析鉴定和纯化,最终获得Exendin-4,产率为21%,纯度为99.4%。活性测定结果显示,合成的Exendin-4显著提高胰岛瘤细胞的活性,并呈一定剂量依赖性。
Exendin-4 is the first approved pancreatic hormone analogue drug to simulate the body’s own hormone GLP-1 function, not only improve blood sugar, but also promote pancreatic β-cell neonatal proliferation, inhibition of β-cell apoptosis and improve β Cell function, promote insulin secretion, increase the body’s sensitivity to insulin. Based on the potential market value of Exendin-4, based on the Fmoc solid-phase synthesis strategy, NMP is the reaction solvent and HOBt / DIC is used as the condensing agent. The cap procedure is added to optimize the synthesis conditions. The peptide resin was cleaved with TFA / Phenol / TIS lysate and analyzed by HPLC and quadrupole-time of flight tandem mass spectrometry to finally identify and purify Exendin-4 with a yield of 21% and a purity of 99.4 %. Activity assay results showed that the synthetic Exendin-4 significantly increased the activity of pancreatic islet cells in a dose-dependent manner.