Exendin-4的固相化学合成及鉴定  

Solid Phase Peptide Synthesis and Analysis for Exendin-4

作　　者：刘延杰[1] 季虹[1] 林鲁霞[1] 臧学章[1] 宋长征[1] 荣海钦[1] 

机构地区：[1]山东省内分泌与代谢病研究所山东省医学科学院,济南250062

出　　处：《中国生物工程杂志》2011年第2期69-73,共5页China Biotechnology

基　　金：山东省科技攻关计划(2009GG20002046;2009GG20002049)资助项目

摘　　要：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 drug of the incretin mimetic family, which acts like the naturally occurring hormone GLP-1 in vivo. Exendin-4 decreases fasting and postprandial plasma glucose levels. Exendin- 4 may play a role in enhancing glucose-dependent stimulation of insulin secretion, and maintaining of β-cell mass by promotion of β-cell proliferation and neogenesis, and inhibiting of β-cell apoptosis. This experiment studied the standard Fmoc strategy solid phase synthesis of Exendin-4. Using NMP as the coupling solvent, HOBt/DIC as the coupling reagent, AIM as the containing reagent. Synthesized peptides were elearaged by TFA/Phenol/TIS, and identified by high performance liquid chromatography and quadrupole time of flight LC/MS. The yield of pure Exendin-4 was 21% with a purity of 99.4%. Using the SRB method to measure the bioassay of Exendin-4 cell regeneration experiment. It is an influential research into the therapy of type 2 diabetes mellitus.

关 键 词：EXENDIN-4 固相化学合成 2型糖尿病 

分 类 号：Q819[生物学—生物工程]