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Polypeptide specifically binding to CD123 protein, polypeptide complex, co-delivery system, preparation method and application thereof

A polypeptide complex and specific technology, applied in the field of biomedicine, can solve problems such as outstanding curative effects that have not yet been observed, and achieve the effects of easy synthesis and modification, inhibition of activity, and inhibition of interaction

Active Publication Date: 2022-03-22
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 specifically binding to CD123 protein, polypeptide complex, co-delivery system, preparation method and application thereof
  • Polypeptide specifically binding to CD123 protein, polypeptide complex, co-delivery system, preparation method and application thereof
  • Polypeptide specifically binding to CD123 protein, polypeptide complex, co-delivery system, preparation method and application thereof

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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 specifically binding to CD123 protein, a polypeptide complex, a co-delivery system and a preparation method and application thereof. The general formula for the arrangement of amino acids in the polypeptide is X 1 ‑DYDTR‑X 2 ‑QGTD‑X 3 ‑G‑X 4 ‑DFRRISD‑X 5 ; Can bind to CD123 positive cells and inhibit the development of leukemia; the polypeptide complex can increase the number of binding of the polypeptide to CD123 positive cells, and a single drug can inhibit the development of leukemia and prolong the survival period of leukemia mice; the co-delivery system can Loading chemotherapeutic drugs for tumor treatment reduces the toxicity of chemotherapeutic drugs to normal cells.

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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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00C07K7/08A61K9/107A61K38/10A61K38/16A61K47/24A61K47/32A61K47/34A61K47/42A61K31/4745A61K31/475A61K31/675A61K31/704A61P35/02
CPCC07K14/001C07K7/08A61K9/1075A61K47/42A61K47/34A61K47/24A61K47/32A61K31/475A61K31/704A61K31/4745A61K31/675A61P35/02A61K38/00A61K2300/00A61K45/06C07K16/2896
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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