转铁蛋白融合技术：一种延长肠降血糖素肽生物半衰期的新方法。
Transferrin fusion technology: a novel approach to prolonging biological half-life of insulinotropic peptides.
机构信息
National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
出版信息
J Pharmacol Exp Ther. 2010 Sep 1;334(3):682-92. doi: 10.1124/jpet.110.166470. Epub 2010 May 24.
Abstract
Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic beta-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides.
摘要
融合蛋白由胰高血糖素样肽 1 (GLP-1) 和 exendin-4 (EX-4) 与非糖基化形式的人转铁蛋白 (GLP-1-Tf 或 EX-4-Tf) 融合而成，并对其进行了特性分析。GLP-1-Tf 能激活 GLP-1 受体，不易被肽酶失活，半衰期约为 2 天，而天然 GLP-1 的半衰期为 1 至 2 分钟。GLP-1-Tf 在糖尿病动物中保留了天然 GLP-1 的急性、葡萄糖依赖性胰岛素分泌特性，并对胰岛 β 细胞的增殖有显著影响。此外，Tf 和融合蛋白不能穿过血脑屏障，但在周围给药后仍能减少食物摄入。EX-4-Tf 的效果与 EX-4 一样，但对血糖和食物摄入的影响持续时间更长。这种新型转铁蛋白融合技术可以改善各种肽类的药理学特性。
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