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Polypeptide and application thereof to preparation of medicament for treatment and/or prevention of tumor

A technology for drugs and tumors, applied in anti-tumor drugs, drug combinations, peptide/protein components, etc., can solve problems such as low biological stability, and achieve the effects of less toxic and side effects, significant curative effect, and safe use

Active Publication Date: 2017-12-15
胡卓伟
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a kind of polypeptide and its preparation for treating and / or preventing tumors in view of the current situation of lack of highly active and highly selective synthetic polypeptide drugs targeting to increase the number of PML nucleosomes. application in medicine
The defect of low biological stability is directly related to the inability of polypeptide S160 to stabilize the α-helical conformation required for activity in solution

Method used

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  • Polypeptide and application thereof to preparation of medicament for treatment and/or prevention of tumor
  • Polypeptide and application thereof to preparation of medicament for treatment and/or prevention of tumor
  • Polypeptide and application thereof to preparation of medicament for treatment and/or prevention of tumor

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Embodiment 1

[0042] The synthesis of embodiment 1 polypeptide

[0043] For the amino acid sequence of the polypeptide S160, see SEQ ID No.1 in the sequence listing. Peptide S160 was synthesized and purified by Beijing Saibaisheng Gene Technology Co., Ltd.

[0044] Two unnatural amino acids S-pentylalanine (S5) were introduced for solid-phase polypeptide chain synthesis. After the solid-phase polypeptide chain is synthesized, ruthenium is used as a catalyst to perform olefin metathesis reaction (RCM) cyclization to obtain the target polypeptide. Finally, the target polypeptide is cleaved from the resin for purification. The steps of solid-phase polypeptide chain synthesis and purification were completed by China Peptide Biochemical Co., Ltd. Among them, two S-pentylalanines are inserted into the i, i+4 positions in the amino acid sequence of the polypeptide A2, thereby obtaining modified polypeptides of different sequences (for the amino acid sequence, please refer to the sequence table ...

Embodiment 2

[0057] Embodiment 2 Circular dichroism method detects the α-helix rate of polypeptide

[0058] The α-helix rate of the polypeptide was detected with a circular dichroism spectrometer (purchased from Jasco, Japan). The polypeptides S160, S160-S1, S160-S2, S160-S3, S160-S4, S160-S5, S160-S6, S160-S7, S160-S8, S160-S9, S160-S10 and S160-S11 was dissolved in the aqueous solution, and the concentration of the circular dichroism spectrometer was adjusted to 1 mg / mL. The results are shown in Table 1. Wherein, the α-helix rate refers to the percentage of the number of peptides of the polypeptide that maintains the secondary structure α-helix to the number of peptides of the total polypeptide.

[0059]Table 1 illustrates that the alpha The helical rate is significantly higher than that of the polypeptide S160. Since the maintenance of the α-helical rate of the polypeptide is an important indicator for increasing the stability of the polypeptide, the increase of the α-helical rate of ...

Embodiment 3

[0062] Example 3 Immunofluorescent staining verification of polypeptides S160, S160-S1, S160-S2, S160-S3, S160-S4, S160-S5, S160-S6, S160-S7, S160-S8, S160-S9, S160-S10 and S160-S11 targeting increases the number of PML nucleosomes

[0063] The specific operation steps are as follows:

[0064] 1. HepG2 liver cancer cells in the logarithmic growth phase (purchased from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences) were collected, and the cell concentration was adjusted with DMEM medium (purchased from Invitrogen, USA) to make a cell suspension of 150,000 cells / mL.

[0065] 2. Add 1 mL of the cell suspension prepared in step 1 into a 12-well plate (the cell culture glass discs are added to the 12-well plate in advance, and the cell culture glass discs are purchased from (Beijing Haide Venture Biotechnology Co., Ltd.) for cultivation, 12 Change to a new medium after 1 hour, and add 1 μg / mL of the polypeptides S160, S160-S1, S160-S2, S160-S3, S160-...

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Abstract

The invention provides a polypeptide and an application thereof to preparation of medicament for treatment and / or prevention of tumor. An amino acid sequence of the polypeptide is shown in a sequence table SEQ ID No.1, or shown in the sequence table SEQ ID No.1 amino acid sequence with two or more amino acids substituted by unnatural amino acids with connectable side chains, and a derivative comprises a chimeric peptide formed by connection of the polypeptide and a cell-penetrating peptide, a fusogenic peptide formed by the polypeptide and a virus, a methylated polypeptide, a glycosylated polypeptide, and a pegylated polypeptide. The polypeptide or the polypeptide derivative can targetedly increase number of PML nucleosomes, and can be applied to preparation of medicament for treatment and / or prevention of tumor.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a polypeptide and its application in preparing medicines for treating and / or preventing tumors. Background technique [0002] The tumor suppressor PML (Promyelocytic leukemia protein, PML) has always been a research hotspot in the scientific community because it is related to the pathogenesis and disease progression of acute promyelocytic leukemia (APL). The PML gene located on chromosome 15 is fused with the RARα gene located on chromosome 17 to encode the fusion protein PML-RARα, which is the main carcinogenic factor of APL. The PML gene contains 9 exons and spans 53kb in the whole genome. Due to the different breakpoints of the PML gene, there are 6 nuclear and 1 cytoplasmic PML isoforms. Among them, PML-I is the longest isomer, consisting of 882 amino acids; PML VII is the shortest isomer, consisting of 435 amino acids. The N-terminal 418 amino acids of the amino a...

Claims

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Application Information

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IPC IPC(8): C07K7/08A61K38/10A61P35/00
CPCA61K38/00C07K7/08A61P35/00
Inventor 胡卓伟李珂王凤
Owner 胡卓伟
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