Application of novel peptide (Pp1) improving the half-life of exendin-4 in vivo

作者：Zheng Xuemin; Li Ying; Fu Gang; Gong Min^*

来源：Peptides, 2011, 32(5): 964-970.

DOI：10.1016/j.peptides.2011.02.009

• Exendin-4
• Long-lasting anti-diabetes
• HbA(1c)
• Biological half-life

Aims: The multiple physiological characterizations of exendin-4 make it as a promising drug candidate for the therapy of type 2 diabetes. Although the longer biological half-life offered the exendin-4 with excellent therapeutic potentials for the clinical utility of type 2 diabetes than glucagon-like peptide-1, the exendin-4 still did not free from the inconveniently frequent injections. Therefore, there are increasing requirements for the long-acting exendin-4.
Methods: Pp1 regard as a novel exendin-4 protecting peptide, which are predicted to have the ability of increasing the stabilization of exendin-4 in vivo. Protecting peptide is able to form stable complex by non-covalent interaction with human exendin-4.
Results: In this study, the stability of the exendin-4/Pp1 complex was investigated, and the physiological functions of it were analyzed. Results indicated that exendin-4/Pp1 complex remarkably raised the stabilization of exendin-4 in vivo: it also showed better glucose tolerance and higher HbA(1c), reduction than exendin-4 which was utilized chronically in rodents.
Conclusion: Based upon these results, it is suggested that an exendin-4/Pp1 complex might be utilized as a potent anti-diabetic drug in the treatment of type 2 diabetes mellitus.

• 出版日期2011-5
• 单位天津药物研究院有限公司; 天津中医药大学