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A liver cancer targeting ruthenium complex and its preparation method and application

A ruthenium complex, liver cancer technology, applied in the field of medicine, can solve problems such as lack of tumor targeting, achieve good anti-cancer effect, improve water solubility, and good biocompatibility.

Active Publication Date: 2021-08-03
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of the deficiencies in the prior art above, the purpose of the present invention is to provide a liver cancer-targeting ruthenium complex and its preparation method and application, aiming to solve the problem that the existing metal anti-tumor drugs lack tumor targeting

Method used

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  • A liver cancer targeting ruthenium complex and its preparation method and application
  • A liver cancer targeting ruthenium complex and its preparation method and application
  • A liver cancer targeting ruthenium complex and its preparation method and application

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preparation example Construction

[0040] The present invention also provides a preferred embodiment of the preparation method of the aforementioned liver cancer-targeted ruthenium complex, the preparation process is as follows: figure 1 shown, including:

[0041] Step A, synthetic peptide

[0042] Step B, connecting β-alanine to the N-terminus of the polypeptide to obtain

[0043] Step C, adding the carboxyl-containing ruthenium complex and the product obtained in step B to the reactive agent for reaction, and purifying the product to obtain

[0044] The present invention selects a ruthenium complex (Ru) with an active carboxyl structure (-COOH) and a polypeptide with liver cancer targeting, and designs between the two, which can improve the water-soluble β-alanine of the product, and finally synthesizes a protein with liver cancer targeting Oriented ruthenium complexes (Ru-T-Pep).

[0045] In the present invention, the polypeptide can be of any structure type, and a preferred polypeptide is HCBP1 (se...

Embodiment 1

[0053] Embodiment 1 (reaction process is as figure 2 shown)

[0054] (1) Solid-phase synthesis of polypeptides is prepared by Rink-Amide-MBHA-Resin resin (10eq, degree of substitution: 0.53mmol / L). Nitrogen gas is passed through at room temperature, and the reaction is carried out by bubbling. The amino acids with Fmoc protection are sequenced FQHPSFI sequential synthesis of peptides.

[0055] (2) Using HCTU (1eq) and DIPEA (0.5eq) as a coupling agent, link the β-Ala amino acid to the N-terminus of the above polypeptide to obtain FQHPSFI-β-A-NH 2 , mass confirmed that the target product with m / z 473.5 was obtained.

[0056](3) Condensation reaction The product of step (2) is mixed with ruthenium complex (1.2eq), HoBt (3eq), PyBop (3eq) and DIPEA (3eq), and the reaction is carried out under nitrogen for 10 hours. In the ruthenium complex The carboxyl group of β-alanine undergoes a coupling condensation reaction with the amino group in β-alanine. The above crude product was...

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Abstract

The invention discloses a liver cancer-targeting ruthenium complex and its preparation method and application. The general structural formula of the liver cancer-targeting ruthenium complex is: wherein, is a ruthenium complex; and is a polypeptide group. Tests show that the liver cancer-targeting ruthenium complex of the present invention can selectively target liver tumor cells, that is, it has a good anticancer effect on liver cancer cells, but basically has no toxicity to normal cells.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a liver cancer-targeting ruthenium complex and its preparation method and application. Background technique [0002] Malignant tumors are obviously tissue invasive, causing tumor tissue to be mixed with normal tissue. Currently, non-targeted chemotherapy in clinical practice often causes damage to normal tissue, causing huge toxic and side effects to patients. Only targeted therapy can achieve this goal. optimal therapeutic effect. Because targeted drugs can selectively gather at the tumor site, and then specifically kill tumor cells without affecting the normal tissues around the tumor, thereby improving efficacy and reducing side effects. [0003] Currently used metal anti-tumor drugs, such as cisplatin and oxaliplatin, lack tumor targeting, which leads to serious side effects and great pain for patients during treatment. [0004] Therefore, the prior art still needs to be i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06C07K1/107C07K1/14A61K38/08A61P35/00
CPCA61K38/00A61P35/00C07K7/06
Inventor 张平玉王祎张黔玲刘剑洪
Owner SHENZHEN UNIV