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Derivative of vascular endothelial growth factor receptor antagonistic peptide F56 and application thereof

A technology of growth factor receptor and vascular endothelium, which is applied in the field of derivatives of vascular endothelial cell growth factor receptor antagonist peptide F56, can solve the problems of short half-life and achieve the effects of prolonged action time and good stability

Active Publication Date: 2018-10-09
BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, although the polypeptide F56 has shown good anti-angiogenesis and tumor growth and metastasis inhibitory effects in in vivo and in vitro experiments, its half-life is too short, which is an important problem in its clinical application.

Method used

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  • Derivative of vascular endothelial growth factor receptor antagonistic peptide F56 and application thereof
  • Derivative of vascular endothelial growth factor receptor antagonistic peptide F56 and application thereof
  • Derivative of vascular endothelial growth factor receptor antagonistic peptide F56 and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1, Preparation and Identification of F56 Modified Peptide

[0047] In this example, polypeptide F56 and F56 N-terminal modified peptide F56-AM ( figure 1 ), middle region modified peptide F56-BM ( figure 2 ) and carboxy-terminal modified peptide F56-CM ( image 3 ).

[0048] Modified peptide synthesis raw materials and related reagents, instruments:

[0049] 1. Resin: 2-Chlorotrityl Chloride Resin with a substitution degree of 1.03mmol / g (Tianjin Nankai Synthetic Technology Co., Ltd.);

[0050] 2. Amino acids: Fmoc-Gly-OH (Chengdu Chengnuo, >99%), Fmoc-Leu-OH (Chengdu Chengnuo, >99%), Fmoc-Tyr(Tbu)-OH (Chengdu Chengnuo, >99% ), Fmoc-Trp(Boc)-OH (Chengdu Chengnuo, >99%), Fmoc-Glu(OtBu)-OH (Chengdu Chengnuo, >99%), Fmoc-Met-OH (Chengdu Chengnuo, >99%) %), Fmoc-Asp(OtBu)-OH (Chengdu Chengnuo, >99%), Fmoc-Ser(tBu)-OH (Chengdu Chengnuo, >99%), Fmoc-His(Trt)-OH (Chengdu Chengnuo, >99%), Fmoc-His(Trt)-OH (Chengdu Chengnuo promise, >99%);

[0051] 3. Raw materia...

Embodiment 2

[0135] Example 2, F56 modified peptide can bind to human serum albumin in vitro

[0136] In this example, it was confirmed by in vitro experiments that the F56-AM, F56-BM, and F56-CM of the present invention prepared according to the method of Example 1 can bind to human serum albumin.

[0137] Experimental steps:

[0138] (1) Prepare 25% human serum albumin (3.79mM) solution: Weigh 0.25g of human serum albumin into a 1.5mL sterile Eppendorf tube, add 750μL of sterile phosphate buffer (100mM NaH 2 PO 4 / Na 2 HPO 4 , pH=7.4), vortexed to mix, and set the volume to 1.0 mL. No sonication was performed.

[0139] (2) Preparation of 10 mM polypeptide F56-AM / F56-BM / F56-CM-dimethylsulfoxide (DMSO) solution: dissolve the above polypeptide to 10 mM with DMSO.

[0140] (3) Preparation of polypeptide reaction solution: the above two solutions were mixed at a volume ratio of 9:1 (human serum albumin:modified peptide) to obtain a reaction solution corresponding to a molar ratio of 3:1...

Embodiment 3

[0151] Example 3, Study on the Activity of F56 Modified Peptides at Different Sites

[0152] 1. Tube Formation Experiment of Endothelial Cells

[0153] In this example, Matrigel was used to simulate the basement membrane of mammalian cells in vitro, and the differences in the formation of three-dimensional tubular structures on the extracellular matrix of human umbilical vein endothelial cells (HUVEC) with different treatments were observed.

[0154] Experimental steps of endothelial cell tubular structure formation:

[0155] (1) Pre-thaw Growth Factor Reduced Matrigel (BD company product number: 356230) on ice at 4°C, and pre-cool the 96-well plate and pipette tips at 4°C.

[0156] (2) Place the 96-well plate on ice, spread 50 μl of Matrigel on each well, and incubate at 37° C. for 30 minutes.

[0157] (3) Digest HUVEC primary cells, count, dilute to 10000 cells / 100 μl with serum-free medium, add final concentration of 0.1% BSA and 20ng / ml VEGF.

[0158] (4) F56-AM, F56-BM...

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PUM

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Abstract

The invention provides a derivative of a vascular endothelial growth factor receptor antagonistic peptide F56 and application thereof. The derivative of the vascular endothelial growth factor receptorantagonistic peptide F56 provided by the invention is a peptide derivative constructed by connecting a MIPA-AEEA-group on the basis of the structure of the vascular endothelial growth factor receptorantagonistic peptide F56. In addition to maintaining the antagonistic effect of the F56 on the binding of a vascular endothelial growth factor (VEGF) to a receptor 1 (VEGFR1) thereof and having anti-angiogenesis and anti-tumor activities, the peptide derivative has remarkably longer action time than a polypeptide F56, and can be used in anti-angiogenesis and anti-tumor therapy.

Description

technical field [0001] The present invention relates to a derivative of vascular endothelial cell growth factor receptor antagonistic peptide F56 and its application, specifically, the present invention relates to a derivative of vascular endothelial cell growth factor receptor antagonistic peptide F56, the derivative of the derivative The preparation method and the application of the derivative in the fields of anti-angiogenesis and anti-tumor therapy. Background technique [0002] The growth and metastasis of malignant tumors depend on the formation of new blood vessels. Without the formation of blood vessels, the tumor will be in a "dormant" state with a diameter of less than 1.5-2mm for a long time. The anti-angiogenesis treatment strategy has the characteristics of broad anti-tumor spectrum, less drug resistance and easy access to the target site, so this strategy has been considered as one of the most promising methods for tumor treatment. Anti-angiogenesis drugs such...

Claims

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Application Information

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IPC IPC(8): C07K19/00C07K1/107A61K38/08A61K38/10A61P35/00A61P35/04
CPCA61K38/00C07K7/06C07K7/08C07K14/765C07K2319/00
Inventor 寿成超赵传科冯君楠王立新
Owner BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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