Ampsource Biopharma Shanghai Inc.

Zhao Dong

Qiang Li

Si Ruo Chen

Yuncheng Zheng

Yuanli Li

Xinlu Ma

Yongjuan Gao

Lu Yang

Naichao Sun

Zhu Wang

Zirui Li

Shixiang Jia

Chi Zhou

Jiyu Zhang

Xiong Feng

The present disclosure relates to a dual-function protein for regulating blood glucose and lipid metabolism, wherein said dual-function protein comprises a human GLP-1 analog and human FGF21. In the present disclosure, provided is a method for preparing said dual function protein, and also provided is the use of said dual-function protein in the preparation of a biological substance for treating type 2 diabetes, obesity, dyslipidemia, fatty liver disease and/or metabolic syndrome. The dual-function protein provided in the present disclosure can synergistically regulate blood glucose and lipid levels in vivo, and satisfy multiple requirements for patients with type 2 diabetes such as lowering blood glucose, relieving hepatic steatosis, reducing body weight and improving metabolic disorders of circulating lipids.

Dual-function protein for lipid and blood glucose regulation

A linker peptide for constructing a fusion protein. The linker peptide comprises a flexible peptide and a rigid peptide. The flexible peptide consists of one or more flexible units. The rigid peptide consists of one or more rigid units. The flexible unit comprises two or more amino acid residues selected from Gly, Ser, Ala, and Thr. The rigid unit comprises a human chorionic gonadotropin &#x3b2;-subunit carboxy-terminal peptide (CTP) bearing a plurality of glycosylation sites. The linker peptide can more effectively eliminate mutual steric hindrance of two fusion molecules, decreasing a reduction/loss of polymerization or activity resulting from improper folding of an active protein or a conformational change. On the other hand, the negatively charged, highly sialylated CTP can resist renal clearance, further prolonging a half-life of a fused molecule and enhancing bioavailability of a fused protein. Furthermore, a protective effect of a glycosylated side chain CTP can lower the protease sensitivity of the linker peptide, making a linker region of the fusion protein less degradable.

Linker peptide for constructing fusion protein

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Shanghai, China

Zhao Dong