截短胰高血糖素样肽-1的构象研究

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-1 C端片段, 能获得作用时间长、效力高的GLP-1类似物.

Conformation Research of Shorted Glucagon-like Peptide-1

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.