Modified blood vessel endothelium growth factor polypeptide segment and application thereof

Abstract

The invention discloses an improved endothelium growth factor polypeptide fragment of blood vessel and an application thereof. A polypeptide amino acid, the sequence of which is AHKRKRKKRHYK, compete with and antagonize the promotion effect of angiogenesis of VEGF by the distinguished combination with a VEGF acceptor and are used to prepare anti-tumor angiogenesis drugs; moreover, radionuclide marks used to prepare tumor nuclide developing drugs and internal irradiation of radioactive nuclide drugs can be further made; the appetency between the polypeptide of the invention and the VEGF acceptor is obviously higher than VEGF125-136; S-acetyl-MAG3 is used as a double function chelating agent to make the radionuclide marks for the polypeptide, and the mark rate is more than 95 percent, moreover, the marks are good in stability, do not need to be purified and can be directly used.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a modified vascular endothelial growth factor polypeptide fragment and its application. Background technique [0002] Angiogenesis is required for normal body activities, including reproduction, development and wound healing. Although angiogenesis is a highly regulated process under normal conditions, many diseases are driven by persistent dysregulated angiogenesis, and these diseases are collectively referred to as angiogenic diseases. For example, neovascularization of the eye is the most common cause of blindness; growth and metastasis of solid tumors are dependent on neovascularization, which involves multiple steps including dissolution of the initial vascular membrane, endothelial cell proliferation and migration, and neovascularization . [0003] Vascular endothelial growth factor (VEGF) is the most important pro-angiogenic factor, it mediates its activity through its recept...

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Problems solved by technology

The study found that radionuclides 188 Re labels the polypeptide VEGF125-136, the marker 188 Re-VEGF125-136 can obviously accumulate in the tumor tissue of tumor-bearing mice, and can be used for SPECT imaging of tumors and inhibition of tumor growth. However, this method has the following disadvantages: ① Using S-acetyl-MAG 3 As a bifunctional chelating agent, radionuclides for VEGF125-136 188 Re labeling, the labeling rate is only about 80%, and it needs to be purified by HPLC before it can be used for imaging and treatment of tumors, which severely limits its clinical and scientific application prospects;② 188 The residence time of Re-VEGF125-136 in tumor tissue is short (substantially subsides within 3 hours), and the killing effect does not last long, which may be due to the low affinity between VEGF125-136 and VEGF receptor

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