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Polypeptide, polypeptide compound and co-delivery system specifically bound with CD123 protein, and preparation methods and applications for polypeptide, polypeptide compound and co-delivery system

A polypeptide complex and specific technology, applied in the field of biomedicine, can solve problems such as outstanding curative effect that has not been observed, and achieve the effects of easy synthesis and modification, prolonging survival period and inhibiting activity

Active Publication Date: 2020-10-02
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the above-mentioned compounds, only SL-401 has been approved by the US FDA as the first CD123-targeted drug, mainly for the treatment of plasmacytoid dendritic cell tumors, and the rest of the drugs are in clinical trials (phase I / II), and No outstanding efficacy has been observed in clinical practice

Method used

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  • Polypeptide, polypeptide compound and co-delivery system specifically bound with CD123 protein, and preparation methods and applications for polypeptide, polypeptide compound and co-delivery system
  • Polypeptide, polypeptide compound and co-delivery system specifically bound with CD123 protein, and preparation methods and applications for polypeptide, polypeptide compound and co-delivery system
  • Polypeptide, polypeptide compound and co-delivery system specifically bound with CD123 protein, and preparation methods and applications for polypeptide, polypeptide compound and co-delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Embodiment 1: polypeptide and its preparation

[0058] The polypeptide targeting CD123 of the present invention is prepared by a standard solid-phase polypeptide synthesis method, and its amino acid sequence is shown in Table 1, all of which are white powders with a purity of ≥98%, preferably numbered 5 in Table 1. # and 6 # The polypeptides with the amino acid sequences shown are PO-6 and PO-6N. In order to verify the effect of the polypeptides of the present invention, the polypeptides shown in Table 1 were prepared into a polypeptide mother solution with a concentration of 1 mM with PBS buffer solution before all experiments.

[0059] The amino acid sequence of table 1 polypeptide of the present invention

[0060] Numbering code name sequence 1 #

[0061] The polypeptides in Table 1 were identified by high performance liquid chromatography and mass spectrometry, and confirmed to be target polypeptides.

Embodiment 2

[0062] Embodiment 2: Polypeptide complex and its preparation

[0063] The preparation method of polypeptide complex comprises the following steps:

[0064] (1) Dissolve 1-50 mg of high molecular polymer and 1 mg of polypeptide in PBS solution, and dissolve by ultrasonic vortexing to obtain solution A; the high molecular polymer is selected from methoxypolyethylene glycol (mPEG)-polycaprolactone (PCL)(mPEG 2000 -PCL 2000 ), distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol 2000 (PEG2000) (DSPE-PEG2000), polyethylene caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus), polyoxyethylene polyoxypropylene One of ether block copolymer (molecular weight ratio of polyoxyethylene and polyoxypropylene is 80:20), polylactic acid-glycolic acid copolymer (PLGA, molecular weight ratio of polylactic acid and glycolic acid is 50:50) or Several, preferably methoxypolyethylene glycol (mPEG)-polycaprolactone (PCL) (mPEG 2000 -PCL 2000 , commercially available), Soluplus ...

Embodiment 3

[0071] Example 3: Co-delivery system and its preparation

[0072] The preparation method of co-delivery system comprises the following steps:

[0073] (1) Dissolving chemotherapeutic drugs (vincristine, doxorubicin hydrochloride, camptothecin, or cyclophosphamide, etc.) Doxorubicin hydrochloride is preferred.

[0074] (2) Mix the chemotherapeutic drug mother solution obtained in step (1) with the above polypeptide complex according to the mass ratio of the chemotherapeutic drug to the polypeptide complex 1: (10-80), mix in a constant temperature water bath at 25-75°C for 20-120min, Solution D is obtained by encapsulating the chemotherapeutic drug in the polypeptide complex.

[0075] (3) Let the solution D stand at room temperature, filter it with a 0.22 μm polyethersulfone water-based filter membrane, remove free drugs, and obtain a co-delivery system formed by polypeptide complexes and chemotherapeutic drugs, with an average hydration particle size of 50-200 nm .

[0076] T...

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Abstract

The invention discloses a polypeptide, a polypeptide compound and a co-delivery system specifically bound with CD123 protein, and preparation methods and applications for the polypeptide, the polypeptide compound and the co-delivery system. The general formula of amino acid arrangement in the polypeptide is X1-DYDTR-X2-QGTD-X3-G-X4-DFRRISD-X5. The polypeptide can be bound with CD123 positive cellsto inhibit the development of leukemia. The polypeptide compound can increase the binding quantity of the polypeptide and the CD123 positive cells; the development of the leukemia can be inhibited bya single drug; and the lifetime of leukemia mice is prolonged. The co-delivery system can be loaded with chemotherapeutic drugs for tumor treatment, and the toxicity of the chemotherapeutic drugs tonormal cells is reduced.

Description

technical field [0001] The present invention relates to the technical field of biomedicine, in particular to a polypeptide specifically binding to CD123 protein, a polypeptide complex formed by the polypeptide and a polymer material, a co-delivery system containing the polypeptide complex, the polypeptide, the polypeptide complex Preparation methods and applications of drugs and co-delivery systems. Background technique [0002] Acute myeloid leukemia (AML) is a common malignant hematological tumor, characterized by abnormal proliferation and differentiation of immature myeloid cells infiltrating in the bone marrow and inhibiting the normal hematopoietic function of the bone marrow, accounting for about 70% of acute leukemias . Because the disease involves a large number of mutated genes, the therapeutic effects of targeted drugs are still very limited. Therefore, chemotherapy is still the main treatment for this disease. [0003] Current AML chemotherapy mostly adopts cyt...

Claims

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Application Information

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IPC IPC(8): C07K14/00C07K7/08A61K9/107A61K38/10A61K38/16A61K47/24A61K47/32A61K47/34A61K47/42A61K31/4745A61K31/475A61K31/675A61K31/704A61P35/02
CPCC07K14/001C07K7/08A61K9/1075A61K47/42A61K47/34A61K47/24A61K47/32A61K31/475A61K31/704A61K31/4745A61K31/675A61P35/02A61K38/00A61K2300/00A61K45/06C07K14/54C07K16/2896
Inventor 许海燕王琛许仕琳杨延莲孟洁刘健温涛
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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