Polypeptide for inhibition of blood vessel neogenesis or growth and application thereof

An angiogenesis and amino acid technology, applied in the field of biomedicine, can solve the problems of low bioavailability of ophthalmic drugs, cumbersome recombinant expression and purification process, and increase the concentration of drug administration, so as to reduce systemic side effects, low cost, and bioavailability high degree of effect

Active Publication Date: 2016-08-17
SHANGHAI FIRST PEOPLES HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Third, based on the above-mentioned main reasons, the bioavailability of ophthalmic drugs is very low; to improve it, the concentration of drug administration needs to be increased
Fourth, although a series of relatively safe endogenous angiogenesis inhibitors have been confirmed successively, such as angiostatin, which consists of plasminogen Kringle domains 1-4 (plasminogen Kringle 1-4) , can significantly inhibit the growth of vascular-dependent tumors, but due to its large molecular weight and complex spatial conformation, there are deficiencies in the prepara

Method used

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  • Polypeptide for inhibition of blood vessel neogenesis or growth and application thereof
  • Polypeptide for inhibition of blood vessel neogenesis or growth and application thereof
  • Polypeptide for inhibition of blood vessel neogenesis or growth and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Example 1: Synthesis and separation and purification of small peptide SK011

[0067] A commercially available SYMPHONY 12-channel polypeptide synthesizer (Protein Technologies, USA) was used to synthesize the SK011 polypeptide whose sequence is shown in SEQ ID NO:23. The specific method is as follows: calculate and configure reagents according to the software (Version. Dikma), shaking for 30min. Filter the solvent through the sand core, add 3-fold molar excess of Fmoc-L-H-OH (Fmoc-leucine-histidine-OH) (small peptide SK011) amino acid (Suzhou Tianma Pharmaceutical Group Fine Chemicals Co., Ltd.) , and then add 10-fold molar excess of DIEA (Shanghai Chemical Reagent Company, Sinopharm Group), and finally add DMF to dissolve, and shake for 30 minutes. Remove DMF, add 20% piperidine (Shanghai Chemical Reagent Company) DMF solution (15ml / g) for 5min, remove DMF, add 20% piperidine DMF solution (15ml / g) for 15min. Take out the piperidine solution, take more than a dozen r...

Embodiment 2

[0074] Example 2: Identification and preservation of the small peptide SK011

[0075] A small amount of the finished small peptide SK011 was taken for purity identification by HPLC analysis and molecular weight identification by ESI-MS. The conditions were as follows: electrospray ionization, detection in positive ion mode, nitrogen as sheath gas, auxiliary gas and sweep gas. Spray voltage 4.7kV: sheath gas 15arb, auxiliary gas 5arb, purge gas 0arb; capillary temperature: 275°C, capillary voltage 40V, lens voltage 120V. Full scan mass range: 300-2000amu. Secondary mass spectrometry was collected in data-dependent mode. The +2-valent molecular ion peak in the full-scan spectrum was used for secondary mass spectrometry analysis. High-purity helium was used as a collision gas with a collision energy of 35 eV.

[0076] The results showed that the small peptide SK011 molecular weight: 1523.83DA, its structural information is correct, conforms to the theoretically designed amino a...

Embodiment 3

[0078] Example 3: Preparation, identification and activity detection of the derivative polypeptide SK001-018

[0079] The polypeptides shown in Table 3 were prepared according to the method of Example 1, and the peptides were identified according to Example 2. The structural information of these polypeptides is correct and consistent with the designed amino acid sequence. And the activity detection was carried out as follows.

[0080] 1. Activity detection principle

[0081] VEGF has the activity of promoting the proliferation of HUVEC cells, and the polypeptide of the present invention has the effect of inhibiting VEGF. Therefore, this test uses HUVEC cells for biological activity comparison. First, HUVEC cells are inoculated, and each sample is diluted with 2% FBS-ECM. After the dilution is completed, Each sample was mixed with VEGF. After the cells adhered to the wall, discard the supernatant in each sample well, add the sample, and make a dilution control and a VEGF con...

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Abstract

The invention belongs to the biological medicine field, and in particular, relates to a polypeptide for inhibition of blood vessel neogenesis or growth, a coding sequence, a vector containing the coding sequence, host cells, pharmaceutical compositions and a pharmaceutical use of the polypeptide. The polypeptide has the advantages of small molecular weight, good water solubility, high safety and good stability, and can be prepared by a solid phase synthesis method; and the purity is high, the yield is high and the cost is low.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a polypeptide for inhibiting angiogenesis or growth. Background technique [0002] The formation of neovascularization is an extremely complex process, which includes: dilation of existing blood vessels, increase of vascular permeability, degradation of perivascular matrix, activation of proliferation and migration of endothelial cells, and formation of new capillary-like lumens. Under normal physiological conditions, angiogenesis is a process closely regulated by multiple links, which plays an important role in repairing and maintaining the normal function of the body. However, if the blood vessels inside the tumor grow rapidly, it is one of the common clinical phenomena. A large number of animal models and human clinical trials have shown that blocking the formation of new blood vessels in tumors can effectively prevent the growth of tumors and trigger the death of tumor...

Claims

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Application Information

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IPC IPC(8): C07K7/06C12N15/12C12N15/85A61K38/08A61P27/02A61P35/00A61P17/06A61P15/08
Inventor 许迅柯潇郑颖邬智刚
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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