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Polypeptide ALKG and application thereof in drugs for treating leukaemia

A leukemia and drug technology, applied in the field of polypeptide ALKG and its application in the treatment of leukemia drugs, can solve the problems of lack of drug resistance in patients with refractory and relapsed cases, and achieve the purpose of inhibiting the growth of leukemia tumor cells and inducing tumor cell Apoptotic effect

Active Publication Date: 2015-01-21
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The application of emerging new chemotherapy drugs, multi-drug combination chemotherapy and hematopoietic stem cell transplantation has greatly improved the prognosis of acute leukemia, but there is still a lack of effective coping strategies for refractory and relapsed cases and drug resistance of patients

Method used

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  • Polypeptide ALKG and application thereof in drugs for treating leukaemia
  • Polypeptide ALKG and application thereof in drugs for treating leukaemia
  • Polypeptide ALKG and application thereof in drugs for treating leukaemia

Examples

Experimental program
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Effect test

Embodiment 1

[0039] In this example, the polypeptide ALKG of the present invention is synthesized by the conventional method Fmoc solid-phase polypeptide synthesis method, and the specific synthesis steps are as follows:

[0040] 1. Connection of the first amino acid Fmoc-Gly-OH with Rink Amide MBHA resin:

[0041] Step 1.1. Weigh 2g (1mmol, 0.5mol / g) of Rink Amide MBHA resin into the reactor, add 10ml of DCM to swell the resin, shake for 2h, and remove the DCM by vacuum filtration to obtain the swollen resin.

[0042] Step 1.2: Dissolve 2.5mmol Fmoc-Gly-OH in 10ml THF and DMF mixture (V:V=11:9), add 3mmol DIC and 2.5mmol HOBt after dissolving, and stir for 30min under ice bath. Then filter to remove the precipitate, add the filtrate to the swollen resin obtained in step 1.1, add 0.5 mmol DMAP, and react at room temperature for 4 h. The reaction solution was removed by vacuum filtration to obtain a Gly-bound resin, which was washed with DMF, DCM, and MeOH three times, each time for 3 min....

Embodiment 2

[0053] Mass spectrometric identification and RP-HPLC analysis of polypeptide ALKG of the present invention:

[0054] ESI-MS mass spectrometry: the detection method is positive ion detection. The detection result of the polypeptide ALKG prepared in Example 1 is: [M+H] + =1238.80 (the molecular weight of polypeptide ALKG is 1238.57). The results of mass spectrometry were in line with the prediction, and the product could be determined to be the polypeptide ALKG. The results were as follows: figure 1 shown.

[0055] RP-HPLC analysis: Take 1 mg of ALKG peptide purified product, dissolve it in 1 ml of double-distilled water, and filter it through a filter membrane with a diameter of 0.22 μm for analysis. Liquid phase analysis conditions: chromatographic analysis column (4.6*250mm, phenomenonex C18-5); mobile phase A: 0.1% TFA in 100% CH 3 CN; mobile phase B: 0.1% TFA in 100% H 2 O, flow rate: 1.0ml / min, detection wavelength 220nm. The analytical gradient was 36-61% A in 25 mi...

Embodiment 3

[0057] Antitumor activity experiment of polypeptide ALKG of the present invention:

[0058] A.MTT experiment.

[0059] Cultivate leukemia cell lines HL60 and U937 and normal PBMC cells. After the cells grow to the logarithmic phase, add 100 μM, 10 μM, 1 μM, 0.1 μM of the polypeptide ALKG of the present invention, 5% CO 2 , 37°C and incubated for 24h, 48h, and 72h, respectively, and MTT method was used to detect the growth inhibitory effect of the capture peptide on normal cells and leukemia cell lines.

[0060] As shown in FIG. 3 , the tumor suppressive activity of the polypeptide ALKG of the present invention increases with the increase of the dosing time, but has no obvious inhibitory effect on normal PBMC cells. At 100μM, the polypeptide ALKG has obvious inhibitory effect on the growth of leukemia cells HL60 and U937 (P≤0.05). At 100 μM peptide concentration, the 24h, 48h, and 72h tumor inhibition rates of the polypeptide ALKG for HL60 were 46.33%, 50.79%, and 59.75%, res...

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Abstract

The invention discloses a polypeptide ALKG of which the amino acid sequence Lys-Phe-Val-Cys-Gly-Val-Ser-Leu-Cys-Leu-Leu-Gly and the molecular weight is 1238.57. The invention also discloses application of the polypeptide ALKG in preparing drugs for leukaemia. The invention also discloses application of the polypeptide ALKG in drugs for treating leukaemia. The polypeptide ALKG does not have homology with the existing antitumor polypeptide, and can inhibit the leukaemia tumor cells from growth and induce the apoptosis of the tumor cells when acting on the leukaemia cell line, thereby providing new drug candidates and material basis for broad-spectrum high-efficiency low-side-effect targeted leukaemia treatment strategies.

Description

technical field [0001] The invention belongs to the technical field of polypeptide drugs in biochemistry, and in particular relates to a polypeptide ALKG and its application in drugs for treating leukemia. Background technique [0002] Leukemia is a group of highly heterogeneous hematological malignancies, belonging to clonal diseases of hematopoietic stem cells. Leukemic cells lose the ability to further differentiate and mature, stagnate at different stages of cell development, and accumulate in large numbers in bone marrow and other hematopoietic tissues. And infiltrate other tissues and organs, resulting in the inhibition of normal hematopoietic function, endangering the function of normal organs. According to statistics, leukemia in my country is prone to occur in adolescents, and its incidence rate ranks first among adolescent tumors. The treatment of leukemia has made many new progresses in recent years, but there are still many deficiencies. The application of emer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08A61K38/10A61P35/02
Inventor 张惠中董轲杨龙飞林芳
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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