截短胰高血糖素样肽-1的构象研究

Conformation Research of Shorted Glucagon-like Peptide-1

截短胰高血糖素样肽-1(sGLP-1)不仅具备刺激胰岛β细胞增生和降低血糖的功能,而且半衰期较长,具有非常好的新药开发前景.为了阐明sGLP-1的功能,本文运用圆二色光谱和荧光光谱探究了sGLP-1在不同条件下的构象,结果表明,sGLP-1在磷酸盐缓冲液中主要呈无规则构象,螺旋含量很低;在含十二烷基硫酸钠或三氟乙醇的磷酸盐缓冲液中主要呈螺旋构象.溶液pH值和温度变化对sGLP-1的构象影响显著.sGLP-1保留了结合并激活受体的关键残基,在受体的诱导下,在体内形成正确构象,从而结合并激活受体,发挥它的功能.研究结果表明,适当缩短GLP-1C端片段,能获得作用时间长、效力高的GLP-1类似物.

Shorted glucagon-like peptide-1（ sGLP-1） not only stimulate proliferation of pancreatic beta cells and decrease blood glucose,but also has a longer half-life. This make sGLP-1 has become a potential new drug in the future. In order to elucidate the function of sGLP-1,this study investigates the conformation of sGLP-1 in different conditions by circular dichroism spectrum and fluorescence spectrum. The conformations of sGLP-1 in phosphate buffer are mostly unordered structure and very low helix,and are mostly α-helix in phosphate buffer containing SDS or TFE. Temperature and pH values of solutions have great influences on the conformation of sGLP-1. sGLP-1 preserve the critical residues which are responsible for binding and activating receptor,Induced by receptor,sGLP-1 can form the correct conformation which can bind and activate receptor in vivo,then realize its function. The results show that appropriately truncate C-terminal segment of GLP-1, may obtain long-term and high efficiency GLP-1 analogues.