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Targeted peptide of epidermal growth factor receptor (EGFR) and application thereof

A receptor and targeting technology, applied in the direction of medical preparations containing active ingredients, peptides, polymer compounds, etc., can solve the problem of increasing drug toxicity to the reticuloendothelial system and achieve good EGFR targeting , small molecular weight, convenient synthesis

Inactive Publication Date: 2013-03-27
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, if the lesion is not in the reticuloendothelial system, such preparations will increase the toxicity of the drug to the reticuloendothelial system

Method used

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  • Targeted peptide of epidermal growth factor receptor (EGFR) and application thereof
  • Targeted peptide of epidermal growth factor receptor (EGFR) and application thereof
  • Targeted peptide of epidermal growth factor receptor (EGFR) and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] EGFR contains 3 main autophosphorylation sites that can regulate the activity of EGFR, namely Y1068, Y1148 and Y1173. The method of sequence comparison / structural analysis is used to design the amino acid sequence derived from the three main sites of action as a small molecule peptide ligand targeting EGFR: EY 1068 INQ, PDY 1148 QQD, AEY 1173 LR.

[0041] In order to screen for small active peptides that bind to EGFR with strong specificity, we synthesized FITC-labeled EYINQ, PDYQQD, AEYLR, RALEL (irrelevant peptides), NYQQN (Mineo Abe, et al. Inhibition of Autophosphorylation of Epidermal Growth Factor Receptor by a Small Peptide Not Employing an ATP-Competitive Mechanism, Biopolymers 89(2007) 40-51. ), and selected LARLLT as a control, and LARLLT was also labeled with FITC. Flow cytometry analysis of the above-mentioned peptides and expression of EGFR (NCI-H1299) ( figure 1 A) and almost no expression of EGFR (K562) ( figure 1 B) The binding rate of different cell lines....

Embodiment 2

[0044] In order to further investigate the binding of each peptide to tumor cells, we carried out an endocytosis experiment (FITC-labeled peptide 10μM incubated with NCI-H1299 and K562 cells at 37°C for 1 hour), such as figure 2 As shown, both FITC-AEYLR and FITC-LARLLT can effectively mediate endocytosis, but K562 cells have no such effect. The experimental results are consistent with Example 1.

Embodiment 3

[0046] To further identify whether this targeting ligand has affinity for human lung cancer biopsy specimens, we used immunohistochemistry to test the reactivity of AEYLR and RALEL with lung adenocarcinoma in patients with lung cancer. Prepare paraffin sections of human lung adenocarcinoma, block the endogenous peroxidase activity, and then incubate with biotin-labeled AEYLR and RALEL. Use HRP-streptavidin to detect with conventional immunohistochemical staining, and use EGFR monoclonal antibody as a control.

[0047] The result is image 3 As shown, biotin-labeled AEYLR can recognize tumor cells in human lung adenocarcinoma biopsy specimens, and the color displayed is close to that of EGFR monoclonal antibody, while biotin-labeled irrelevant peptide RALEL cannot bind to lung adenocarcinoma biopsy specimens without obvious Color changes. These data indicate that AEYLR can recognize EGFR on the surface of cancer cells in patients with lung adenocarcinoma.

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Abstract

The invention belongs to the technical field of medicine and relates to a targeted peptide of epidermal growth factor receptor (EGFR) and the application thereof. The design of the invention comes from small peptides of EY1068ING (sequence (SEQ) identity (ID) NO:1), PDY1148QQD (SEQ ID NO:2) and AEY1173LR(SEQ ID NO:3) of main self-phosphorylation acting site of EGFR. The peptide is used for modifying nanometer lipid carriers which comprise solid-state lipid material, lipid-state oil, fat-soluble emulsifier, polyethylene glycol (PEG) modified lipid, water-soluble emulsifier and additive. The peptide has the following characteristics: (1) the obtained polypeptide has small molecular weight, convenient synthesis, low cost, high affinity with EGFR and strong specificity; (2) the obtained small peptides has good EGFR targeting and can be used for constructing the carriers for targeted therapy of tumor with high expression of EGFR.

Description

technical field [0001] The invention relates to a polypeptide targeting EGFR receptors and its application, in particular to its application in a modified nano lipid carrier, which belongs to the field of pharmaceutical preparations. Background technique [0002] Epidermal growth factor receptor (EGFR) is widely distributed on the cell membrane of various human tissues. It is a multifunctional transmembrane glycoprotein and belongs to receptor tyrosine kinase (RTK). Compared with normal cells, the growth of tumor cells, especially EGFR-positive tumor cells, is obviously dependent on EGFR signal transduction, and has a significant down-regulation mechanism defect, and its EGFR expression level can be several thousand times higher than that of normal cells. The signal transduction network of EGFR plays an important role in the formation and development of tumors. It is a promising target molecule for tumor treatment and is a research hotspot. [0003] However, more and more s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K47/42A61K45/00A61P35/00
Inventor 潘卫三韩翠艳杨星钢太玲钰孙明爽李静
Owner SHENYANG PHARMA UNIVERSITY
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