A kind of organometallic ruthenium conjugated protein and its preparation method and application

An organometallic and protein-conjugated technology, which is applied in the field of organometallic ruthenium-conjugated protein and its preparation and application, can solve the problems of inability to meet clinical applications, low targeting and anti-tumor activity, and achieves strong targeting, The effect of high antitumor activity

Inactive Publication Date: 2019-01-15
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, the targeting and antitumor activity of the current organometallic ruthenium compounds in vivo are still low, which is far from meeting the requirements of clinical application.

Method used

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  • A kind of organometallic ruthenium conjugated protein and its preparation method and application
  • A kind of organometallic ruthenium conjugated protein and its preparation method and application
  • A kind of organometallic ruthenium conjugated protein and its preparation method and application

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preparation example Construction

[0016] The preparation method of the organometallic ruthenium conjugated protein provided by the present invention comprises: in a buffer solution with a pH value of 7-8 (preferably 7.2-7.5) and a concentration of 10-100mM (preferably 20-50mM), the organometallic The ruthenium antineoplastic drug is in contact with serum protein, the molar ratio of the organometallic ruthenium antineoplastic drug to serum protein is 1-20:1 (preferably 5-10:1), and the serum protein has an amino acid sequence such as SEQ ID Serum albumin shown in NO: 1 or transferrin whose amino acid sequence is shown in SEQ ID NO: 2.

[0017] In the present invention, the contact conditions are not particularly limited. For example, the contact conditions may include a contact temperature of 30-40°C (preferably 35-37°C), and a contact time of 24-72h (preferably for 45-50h).

[0018] In the present invention, the organometallic ruthenium conjugated protein prepared by using at least one of the parameter values...

Embodiment 1-3

[0032] In the buffer solution, the organometallic ruthenium antineoplastic drugs (organometallic ruthenium compounds (2)-(8)) are contacted with serum proteins (serum albumin or transferrin) respectively to obtain serum albumin and organometallic ruthenium Organometallic ruthenium-conjugated proteins of compounds (2)-(8) (denoted by HA-2 to HA-8, respectively) and organometallic ruthenium-conjugated proteins of transferrin and organometallic ruthenium compounds (2)-(8) (represented by Tf-2 to Tf-8 respectively), unbound organometallic ruthenium antineoplastic drugs were removed by centrifugal ultrafiltration through a 10kDa ultrafiltration tube (centrifuged three times at 4°C), the centrifugal force was 5000g, and the centrifugation time was 12min. Among them, the specific parameters such as the buffer solution, the type and dosage of the organometallic ruthenium antineoplastic drug and serum protein, the contact temperature, and the contact time are shown in Table 1 below.

...

Embodiment 4

[0036] The organometallic ruthenium conjugated protein was prepared according to the method of Example 1, except that the contacting temperature was 4°C.

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Abstract

The invention discloses organic metal ruthenium conjugated protein and a preparation method and application thereof. The method comprises the following steps: enabling an organic metal ruthenium antitumor drug to contact with serum protein in a buffer solution with pH value of 7-8 and concentration of 10-100mM, wherein the molar ratio of the organic metal ruthenium antitumor drug to the serum protein is (1-20):1, and the serum protein is serum albumin of which the amino acid sequence is shown by SEQ ID No:1 or transferrin of which the amino acid sequence is shown by SEQ ID No:2. Through the technical scheme, organic metal ruthenium conjugated protein with strong targeting property and relatively high antitumor activity is obtained, and experimental and theoretical basis is provided for further understanding the transport mechanism and molecular action mechanism of the organic metal ruthenium antitumor drug and preparing nano controlled release metal antitumor drug taking serum protein as a vector.

Description

technical field [0001] The present invention relates to an organometallic ruthenium conjugated protein and its preparation method and application, in particular to a preparation method of an organometallic ruthenium conjugated protein composed of serum albumin or transferrin and an organometallic ruthenium antitumor drug As well as the organometallic ruthenium conjugated protein prepared by the method, and the use of the organometallic ruthenium conjugated protein in the preparation of antitumor drugs. Background technique [0002] The successful application of cisplatin and other platinum-based antitumor drugs has stimulated the development of inorganic medicinal chemistry, so people have turned their attention to the research on the drug activity of other transition metal compounds, among which the research on the activity of ruthenium-based antitumor drugs has attracted the most attention. Ruthenium compounds [(η 6 -arene)Ru(en)Cl]PF 6 (arene = benzene homologue; en = e...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/765C07K14/79A61K47/42A61K31/28A61P35/00
CPCA61K31/555A61K47/643A61K47/644C07K14/765C07K14/79C07K19/00
Inventor 汪福意郭伟罗群李鲜婵
Owner INST OF CHEM CHINESE ACAD OF SCI
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