Fusion protein of liver-targeting peptide and recombinant human endostatin and its preparation method and application

Abstract

The invention discloses a fusion protein of liver-targeting peptide and recombinant human endostatin, its preparation method and application. The present invention selects 19 amino acids that can be specifically combined with the receptor--heparan sulfate proteoglycan HSPG on the surface of liver cells in the conserved I region of the N-terminal of the Plasmodium circumsporozoite protein CSP, and uses genetic engineering to fuse it in The carboxy-terminus of the novel human endostatin nhES with 9 amino acid sequences (MGGSHHHHH) added to the amino-terminus, and the liver-targeting peptide and recombinant human endostatin fusion protein (ES‑CSP) were prepared. The fusion protein is easy to purify, can specifically target the liver to inhibit the formation of new blood vessels, increase the local concentration of the drug at the lesion site, reduce the systemic dosage, and reduce its toxic and side effects. It provides ideas and scientific basis for the clinical development of drugs that target angiogenesis to treat liver cancer, and has great scientific significance and practical value for further improving the treatment level of liver cancer in my country.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and more specifically relates to a fusion protein of liver-targeting peptide and recombinant human endostatin, its preparation method and application. Background technique [0002] Primary liver cancer (HCC) is one of the main malignant tumors in my country, with an annual incidence rate of 10-150 / 100,000 people, second only to lung cancer and gastric cancer, and is the third malignant tumor in my country, with an annual mortality rate of about 34.6 per 100,000 people, second only to lung cancer. Primary liver cancer is also the leading cause of death in patients with cirrhosis. It is also a common disease in the world. Primary liver cancer ranks fifth in the world in terms of incidence of malignant tumors, and ranks third in mortality. At present, there are about 350,000 new cases of primary liver cancer in my country every year, accounting for 55% of the new cases in the world. About 320,...

AI Technical Summary

Problems solved by technology

However, during treatment, Endostar is easy to diffuse and degrade in the body, resulting in a relatively uniform tissue distribution and failing to form an effective anti-tumor concentration at the lesion site. In order to achieve clinical effects, the only way to increase the dose of the drug is; however, increasing the dose will cause more severe Toxic and side effects, such as impaired cardiac function, diarrhea, etc., especially potential adverse effects on angiogenesis in physiological states such as embryogenesis and wound healing

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