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Factor VIII inhibitory polypeptide and application thereof

A technology for inhibiting peptides and factors, applied in the fields of peptides, peptide preparation methods, peptide/protein components, etc.

Inactive Publication Date: 2015-12-23
SUZHOU PULUODA BIOLOGICAL SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At this stage, there are no well-developed factor VIII inhibitors available for the treatment of atherosclerosis

Method used

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  • Factor VIII inhibitory polypeptide and application thereof
  • Factor VIII inhibitory polypeptide and application thereof
  • Factor VIII inhibitory polypeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0011] Chemical Synthesis of Peptides

[0012] Polypeptides were prepared using Fmoc-protected solid-phase synthesis techniques. The synthesis reaction is carried out from the C-terminal to the N-terminal according to the polypeptide sequence, and there are free amino groups on the Rink medium (available from AdvancedChemTech). During each ligation step, the amino acid residues are activated, and the activation mixture contains 4 times as many HBTU, HOBt, DIEA and Fmoc-amino acids as there are free amino groups on the medium. After each amino acid linking reaction, a mixture of pyridine / acetic acid / N-methylimidazole (4:1:0.5) was used to block unlinked free amino groups for 10 minutes. After each amino acid linking reaction and before the next amino acid linking, the Fmoc-group on the medium should be removed, and the Fmoc-group should be removed using dimethylformamide containing 20% ​​piperidine, which takes 15 minutes. Finally, after all amino acid residues are linked seq...

Embodiment 2

[0015] Effects of Factor VIII Inhibiting Polypeptides on Mouse Atherosclerosis Models

[0016] A mouse model of atherosclerosis was established. Forty 8-week-old male C57BL / 6J mice were randomly divided into 4 groups: Group A was the blank control group: fed with common feed; Group B was the model control group: model-making + high-fat feed feeding; Group C Drug intervention group: modeling + high-fat feed + factor VIII inhibitory polypeptide (10mg / kg / d); D is positive drug intervention group: modeling + high-fat feed + rosuvastatin tablets (10mg / kg / d) . 12 consecutive weeks. The mice in group A were fed with common feed, and the mice in groups B, C, and D were fed with high-fat and high-cholesterol feed (containing 15% lard + 0.25% cholesterol) to accelerate the formation of atherosclerosis model. After 12 weeks, the body weight of the mice was recorded, and the effects of peptides on serum cholesterol were detected: serum total cholesterol (TC), triglyceride (tryglyeride,...

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PUM

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Abstract

The invention relates to the field of medicaments, in particular to a polypeptide compound for preventing and treating or preventing atherosclerosis. A factor VIII inhibitory polypeptide is characterized in that the sequence of the factor VIII inhibitory polypeptide is WLWPYLFYVQAVPIQKVQDD; the factor VIII inhibitory polypeptide is prepared by adopting an Fmoc protected solid-phase synthesis technique, and can be covalently linked with an adjuvant which is bovine serum albumin, human serum albumin or polyethylene glycol; the invention also discloses application of the factor VIII inhibitory polypeptide to the treatment of atherosclerosis-related diseases which refer to angor pectoris, myocardial infarction, arrhythmia, cerebral apoplexy, encephalanalosis, resistant hypertension, renal insufficiency and other lesions. The factor VIII inhibitory polypeptide disclosed by the invention can be used for targeted inhibition of a factor VIII and inhibition of blood coagulation, so that an action of preventing or treating the atherosclerosis is realized.

Description

Technical field: [0001] The invention relates to the field of medicines, in particular to polypeptide compounds used for preventing and treating or preventing atherosclerosis. Background technique: [0002] Atherosclerosis (Atherosclerosis) is a harmful state caused by the deposition of fat, thrombus, connective tissue and calcium carbonate in blood vessels (mainly arteries, but also veins). It is characterized by thickening and hardening of the arterial wall, loss of elasticity, and narrowing of the lumen. Symptoms of atherosclerosis are mainly determined by vascular lesions and the degree of ischemia of the affected organs. Aortic atherosclerosis is often asymptomatic. In patients with coronary atherosclerosis, if the stenosis of the coronary artery reaches more than 75%, angina pectoris, myocardial Infarction, arrhythmia, and even sudden death. Cerebral arteriosclerosis can cause cerebral ischemia, brain atrophy, or cause cerebral blood vessel rupture and bleeding. Rena...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K1/06A61K38/10A61P9/10A61P9/06A61P9/12A61P13/12
Inventor 罗瑞雪
Owner SUZHOU PULUODA BIOLOGICAL SCI & TECH
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