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Gip and glp-1 double agonist polypeptide compound, pharmaceutically acceptable salt and use
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A technology of GLP-1 and peptide compounds, applied in the direction of hormone peptides, organic chemistry, hormone receptors, etc., can solve the problems of prolonging the half-life of peptides, achieve hypoglycemia and slow down weight gain, low production cost, long drug effect time Effect
Active Publication Date: 2021-12-10
HANGZHOU HEALTHYTIDE BIOTECHNOLOGY CO LTD
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Although the use of fatty acids can improve the half-life of the peptides, applicants discovered that, as part of the present invention, the length, composition and location of the fatty acid chains and the linker between the peptide and the fatty acid chains may have unexpected effects on GIP and GLP-1 agonist activity Balanced effects while prolonging the half-life of the peptide
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Embodiment 1
[0090] Embodiment 1, the synthesis of SEQ ID NO: 1 polypeptide compound:
[0094] Weigh 10g of Fmoc-Rink Amide AM Resin (degree of substitution 0.35mmol / g), swell with 100mL of DCM for 30min, filter to remove DCM, then swell with 100mL of DMF for 30min, rinse with DMF and 100mL of DCM respectively.
[0095] 1.2 Synthesis of Fmoc-Ser(tBu)-Rink Amide AM Resin
[0096]Dissolve Fmoc-Ser(tBu)-OH (8mmol), HOBT (16mmol) and DIC (16mmol) in 100mL of DMF, then add this solution to the resin obtained in the previous step to react for 2 hours, and filter the reaction solution after completion. The resin was washed 3 times with 100 mL each of DCM and DMF.
[0115] The synthesis method was the same as in Example 1, and the collected solution was lyophilized to obtain 1.51 g of pure product.
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Abstract
The invention discloses a class of GIP and GLP-1 double agonist polypeptide compound, which belongs to the technical field of polypeptide medicinal chemistry. The amino acid sequence of this type of GIP and GLP‑1 dual agonist polypeptide compound is: YXaa 1 EGTFTSDYSIXaa 2 LDKIAQXaa 3 AFVQWLIAGGPSSGAPPPS, and the C-terminal amino acid of this type of polypeptide compound is amidated as the C-terminal primary amide. The preparation method, pharmaceutically acceptable salt, pharmaceutical composition and medicament of the polypeptide compound of the present invention. The polypeptide compound of the present invention has both hypoglycemic and weight-reducing effects, and can be used as an effective raw material for preparing medicines for treating or preventing diabetes or weight-loss medicines.
Description
technical field [0001] The present invention relates to the field of polypeptide compounds, in particular to a polypeptide compound with double incretinpeptide analogues, which stimulates the receptors of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) body, and can be used to treat type 2 diabetes. The present invention also relates to the pharmaceutically acceptable salt of the polypeptide compound, the polypeptide pharmaceutical composition, the preparation method of the medicament and the use thereof. Background technique [0002] The cause of metabolic syndrome is abnormal metabolism of various substances such as protein, fat and carbohydrates. Overnutrition and reduced physical activity can lead to obesity and obesity-related diseases such as diabetes. In recent years, the incidence of type 2 diabetes and abnormal blood lipid metabolism has been increasing; type 2 diabetes is the most common form of diabetes, accounting for abo...
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