Application of polypeptide AT03 in drug for treating diabetic nephropathy
A technology of diabetic nephropathy, AT03, applied in the field of biochemistry, can solve problems such as undiscovered drugs and achieve the effect of improving kidney damage
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Embodiment 1
[0027] Embodiment 1, the preparation of polypeptide AT03
[0028] The amino acid sequence of polypeptide AT03 is: Val-His-Val-Val-R 1 ; where R 1 =-NH 2 . In this example, the anti-diabetic polypeptide compound AT03 was synthesized from the carboxy-terminus to the amino-terminus by the Fmoc solid-phase polypeptide synthesis method, and the amino acids of the polypeptide AT03 were connected sequentially according to the aforementioned amino acid sequence.
[0029] (1) Polypeptide synthesis
[0030] The preparation condition of the present invention adopts MBHAR (Amide-MBHA-Resin amide-protected MBHA resin) or Wang resin, and synthesizes by removing the Fmoc protecting group with the method of activating lipid.
[0031] The indene detection reagent of the present invention comprises following components:
[0032] Reagent 1: 20g phenol / 5ml ethanol;
[0033] Reagent 2: 0.05 0.001M KCN (water) / 2.5ml pyridine;
[0034] Reagent 3: 0.5g ninhydrin / 10ml ethanol;
[0035] The u...
Embodiment 2
[0054] Example 2, Study on the therapeutic effect of polypeptide AT03 on mice with diabetes and diabetic nephropathy
[0055] 2.1 The anti-diabetic polypeptide compound AT03 and positive drugs can improve diabetes in diabetic mice
[0056] Obtain the db / db mouse diabetes model (purchased from Nanjing University-Nanjing Institute of Biomedicine, about 12 weeks old, and measure blood sugar and body weight to ensure that the follow-up experiment goes smoothly), and the model mice were randomly divided into 5 groups (normal saline group , AT03 low-dose group, AT03 high-dose group, MED group (MEDI0382, a GLP-1 / GCG receptor dual agonist) and SAR group (SAR425899, a GLP-1 / GCG receptor dual agonist) ), 6 mice in each group, and there was no difference in the basal body weight and blood glucose of each mouse. The mice in each group were subcutaneously injected with compounds AT03 (60 μg / kg), AT03 (120 μg / kg), MED (120 μg / kg), SAR (120 μg / kg), and physiological saline (DN group: normal...
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