ANP32A-targeted anti-leukemia small molecule peptide as well as preparation method and application thereof

A small molecule peptide, leukemia technology, applied in the field of biomedicine, can solve the problems of only about 30-40% cure rate, unoptimistic clinical treatment effect, etc., and achieve the effect of low toxic and side effects

Pending Publication Date: 2021-09-03
WUHAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

With the continuous deepening of people's understanding of leukemia and the advancement of scientific and medical level, the effect of its intervention and treatment has made great breakthroughs since this century. The 5-year survival rate of some types of leukemia can even reach 90%, but the overall cure rate Only around 30-40%
At the same time, the cytogenetics of leukemia has significant heterogeneity, which is closely related to various types of leukemia with poor prognosis, and its clinical treatment effect is still not optimistic

Method used

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  • ANP32A-targeted anti-leukemia small molecule peptide as well as preparation method and application thereof
  • ANP32A-targeted anti-leukemia small molecule peptide as well as preparation method and application thereof
  • ANP32A-targeted anti-leukemia small molecule peptide as well as preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] The pull-down test of competitive inhibition of ANP32A by the small molecule peptide H3BP targeting ANP32A against leukemia

[0056] A. ANP32A protein acquisition, the steps are as follows: cells expressing ANP32A are lysed with cell lysate, centrifuged, cell membrane and other precipitates are removed, and the supernatant is taken, which is the protein solution containing ANP32A.

[0057] B. Prokaryotic expression and purification of 6xHIS tag-tagged histone H3 (6xHIS-H3) and Ni-NTA Resin tweezer beads (DP101-01, full gold) were incubated overnight to obtain complex 1. 6xHIS-H3 can pass through the HIS tag Affinity to Ni-NTAResin tweezer beads for coupling to tweezer beads.

[0058] C. Different concentrations of small molecule peptide TAT-H3BP (0, 0.25, 0.5, 1 mg / L), ANP32A protein solution and complex 1 were incubated together, and TAT was used as a negative control.

[0059] D. After incubation, complexes were obtained by centrifugation. After washing, use SDS-PAG...

Embodiment 2

[0063] Inhibition of Leukemia Cells by Small Molecular Peptide TAT-H3BP

[0064] A. The cultivation of human leukemia cell lines THP1, HL60, K562, and 6133 cells is to be cultivated with RPMI 1640 medium containing 10% newborn bovine serum, with 10 5 The cell density per well was seeded into 24-well cell plates.

[0065] B. Add the fusion peptide (TAT-H3BP) and control polypeptide (penetrating peptide TAT and H3BP not fused to the penetrating peptide) involved in this experiment into the cell culture plate at an appropriate concentration, and use an equal volume of PBS as the blank control Group (Vehicle), 24,

[0066] After 48 and 72 hours, cell counts, that is, cell proliferation detection, were performed.

[0067] C. Experimental results: Compared with the control group, the TAT-H3BP administration group obtained an inhibitory effect on leukemia cells. TAT-H3BP effectively inhibited the proliferation of leukemia cells, while TAT and H3BP control group had no inhibitory e...

Embodiment 3

[0070] In vivo test of small molecule peptide TAT-H3BP inhibiting subcutaneous xenograft tumor of THP1 mice

[0071] A. Experimental animals: SPF grade BALB / c Nude nude mice, a total of 17, provided by Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., the experimental mouse production license number is: SYXK (Beijing) 2017-0033. The rats are 6-7 weeks old and weigh 18-20g. The bedding, drinking water, full-price pellet feed and other articles that come into contact with animals are all autoclaved. The experimental and feeding conditions were strictly in accordance with the requirements of the SPF standard. All animal experiments were approved by the Animal Care and Use Committee of the School of Life Sciences, Wuhan University.

[0072] B. For subcutaneous solid tumor experiments, THP1 cells were injected subcutaneously into the right back of BALB / c nude mice near the axilla as described above, and the wound was pressed without bleeding.

[0073] C. Put the mic...

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Abstract

The invention discloses an ANP32A-targeted anti-leukemia small molecule peptide as well as a preparation method and application thereof, and relates to the technical field of biological medicines. The H3BP peptide fragment can competitively block the combination of ANP32A and unmodified histone H3, and can inhibit the function of ANP32A in promoting leukemia cell proliferation. The H3BP is efficiently brought into leukemia cells in a mode of fusing the cell-penetrating peptide and the H3BP by utilizing the characteristic that the cell-penetrating peptide can carry foreign protein to enter the cells, so that the proliferation of the leukemia cells and the progress of diseases are effectively intervened, and a new solution is provided for effective intervention of leukemia.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a small molecule peptide H3BP targeting ANP32A for anti-leukemia and its preparation method and application. Background technique [0002] Leukemia is a malignant tumor of the blood system, mainly originating from the malignant clonal expansion of hematopoietic stem / progenitor cells in the bone marrow. One of them is characterized by the malignant proliferation of myeloid cells, and the onset is rapid. This type of leukemia is called acute myeloid leukemia (AML); it is characterized by clonal proliferation, abnormally differentiated or poorly differentiated myeloid hematopoietic cells in the bone marrow, Extensive infiltration in blood and other tissues (Short et al., 2018). With the continuous deepening of people's understanding of leukemia and the advancement of scientific and medical level, the effect of its intervention and treatment has made great breakthrou...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C07K19/00C12N15/11A61K38/16A61K47/64A61P35/02A61P7/00A61P35/00A61P31/16A61P31/18A61P37/02A61P29/00
CPCC07K14/00A61K47/645A61K47/64A61P35/02A61P7/00A61P35/00A61P31/16A61P31/18A61P37/02A61P29/00C07K2319/10A61K38/00
Inventor 黄赞王曼曼张昙
Owner WUHAN UNIV
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