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uPAR (urokinase-type plasminogen activator receptor) targeted peptides, probe and living molecular imaging method

A targeting and probe technology, applied in the field of medical imaging, can solve the problems of difficulty in peptide synthesis and high synthesis cost, and achieve the effect of reducing difficulty and synthesis cost, small molecular weight, and easy synthesis

Pending Publication Date: 2018-02-02
HUAZHONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Therefore, the technical problem to be solved by the present invention is to overcome the difficulty and high cost of synthesis of uPAR-targeting polypeptides in the prior art, thereby providing a linear uPAR-targeting polypeptide with a shortened sequence length, while ensuring the specificity of the polypeptide targeting uPAR. On the premise of high stability and high stability, it reduces the difficulty and cost of peptide synthesis targeting uPAR

Method used

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  • uPAR (urokinase-type plasminogen activator receptor) targeted peptides, probe and living molecular imaging method
  • uPAR (urokinase-type plasminogen activator receptor) targeted peptides, probe and living molecular imaging method
  • uPAR (urokinase-type plasminogen activator receptor) targeted peptides, probe and living molecular imaging method

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Embodiment 1

[0053] This embodiment provides a uPAR-targeting polypeptide, that is, the affinity unit in the uPAR-targeting probe.

[0054] "The Receptor-binding Sequence of Urokinase" (E Appella, et. (1987) J.Biol.Chern.Vol.262, No.10, Issue of April 5, pp.4437-4440) reported uPA amino terminal 20- Amino acid residues at position 30 exhibit the ability to specifically bind uPAR, but amino acid residues at positions 20-30 require amino acid residues at positions 13-19 for proper binding conformation. After structural modification of the reported polypeptide, the present invention obtains a linear polypeptide composed of 13 amino acids, which can form a stable binding conformation after entering cells or tissues, specifically recognize and bind uPAR, and bind uPAR high affinity. The above-mentioned uPAR targeting polypeptide is named SY1, the sequence is: Val-Ser-Asn-Lys-Tyr-Phe-Ser-Asn-Ile-His-Trp-Gly-Cys, molecular formula: C 71 h 100 N 20 o 18 S, molecular weight: 1553.7, its struct...

Embodiment 2

[0059] This embodiment provides a uPAR targeting probe, the structure of the uPAR targeting probe is as follows figure 2 As shown, it includes a targeting affinity unit, a signaling unit and a linking unit connecting the affinity unit and the signaling unit.

[0060] 1. Imaging target (uPAR target): it is the receptor uPAR on the cell surface of the serine protease urokinase plasminogen activator (uPA), and uPAR is the main binding target of the probe targeting affinity unit. That is, the target of uPAR targeted imaging.

[0061] 2. Signal unit: it is a part that can be used to affect the detection of equipment. The signal unit of the present invention is selected from radioactive isotopes, and one or more of fluorescent dyes, quantum dots, magnetic materials, and photoacoustic nanoparticles can also be selected.

[0062] (1) Radioactive isotopes: using radioactive divalent or trivalent (M 2+ / M 3+ ) metal ions as signal units, such as 68 Ga, 111 In, 64 Cu, 99 Tc or A...

Embodiment 3

[0074] This embodiment provides a method for preparing uPAR targeting probes, using the radioactive isotope Al 18 F is used as a signal unit, and the chelating agent NOTA is used as a connecting unit. The specific preparation method includes the following steps:

[0075] 1. Preparation of NOTA-SY1

[0076] Mix excess NOTA-Maleimido (5equiv) and SY1 (1equiv) prepared in Example 1 in N,N-dimethylformamide (DMF), and N,N-dimethylformamide (DMF) contains mass The fraction was 1% N,N-diisopropylethylamine (DIPEA), stirred at room temperature for 2 hours. After the reaction solution was directly diluted with water, it was separated and purified by high performance liquid chromatography (HPLC), and the product was identified by mass spectrometry analysis. The reaction formula of NOTA modified SY1 is shown in formula II:

[0077]

[0078] 2. Preparation of Al 18 F-SY1

[0079] Dissolve 10 μg of NOTA-SY1 prepared in step 1 in 0.5 mol / L sodium acetate buffer, then add 5 μL of 2 m...

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Abstract

The invention discloses uPAR (urokinase-type plasminogen activator receptor) targeted peptides with the amino acid sequence indicated in SEQ ID NO. 1. The uPAR targeted peptides is linear peptides formed by 13 amino acids, the peptides are easy to synthesize and can form a stable conformation and be combined with uPARs with specific target. The invention discloses a uPAR targeted probe comprisinga single unit and the above uPAR targeted peptides. The uPAR targeted probe is subjected to specific identification of the peptides and is combined with the uPARs, signals for detection of imaging equipment are transmitted through the signal unit, living visual detection of the uPARs is achieved, and distribution and number of the uPARs are displayed visually and are used for disease detection foruPAR expression abnormalities. The invention further discloses a living molecular imaging method. The uPAR targeted probe is utilized, and the living molecular imaging method has the advantages of being safe, non-invasive, dynamic, visual and the like and is suitable for direct detection of human body.

Description

technical field [0001] The invention belongs to the technical field of medical imaging, and in particular relates to a uPAR targeting polypeptide, a probe and a living body molecular imaging method. Background technique [0002] According to the 2014 World Cancer Report released by the World Health Organization on February 4, 2014, World Cancer Day, cancer has become the largest cause of death for humans all over the world, and the incidence of cancer in China ranks first in the world. With the emergence of various problems such as environmental pollution and food safety, human health is threatened by more and more external environments, which has continuously aggravated the possibility of various cancers. Therefore, how to achieve early diagnosis and personalized diagnosis and treatment of cancer, so as to greatly reduce cancer mortality and improve the quality of life of patients, is an important direction of cancer research at present. [0003] At present, imaging techno...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08A61K47/42A61K51/08A61K49/00A61K49/14A61K49/22A61K103/00A61K103/20A61K103/10A61K101/02
CPCA61K47/42A61K49/0002A61K49/0034A61K49/0065A61K49/0067A61K49/14A61K49/221A61K51/08C07K7/08
Inventor 孙耀杨光富陈琼丁锋陈森李崇录贺小岚
Owner HUAZHONG NORMAL UNIV
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