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Antitumor polypeptide derived from FOXM1 protein

An anti-tumor, penetrating peptide technology, applied in the field of peptide drugs and oncology, can solve the problem of inability to obtain induced pluripotent stem cells

Active Publication Date: 2018-08-24
XINSHENG KANGYUAN BIOPHARML
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, FOXM1 is involved in the maintenance of cell stemness (Nucleic Acids Res 2010. 38: 8027-8038). Inhibition of FOXM1 leads to the inability to obtain induced pluripotent stem cells, which is an essential factor in the reprogramming process of induced pluripotent stem cells (PLoS One 2014 .9:e92304)

Method used

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  • Antitumor polypeptide derived from FOXM1 protein
  • Antitumor polypeptide derived from FOXM1 protein
  • Antitumor polypeptide derived from FOXM1 protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1, the 21-amino acid polypeptide at positions 106-126 in the FOXM1 protein sequence can inhibit the ability to activate transcription of FOXM1.

[0041]1. Construction of a mammalian cell expression vector (pCMV-M1-21) for a 21 amino acid polypeptide (M1-21) at positions 106-126 in the FOXM1 protein sequence. Synthesize the positive and negative strands of double-stranded DNA corresponding to the M1-21 amino acid sequence according to the standard method of DNA synthesis, and include the XbaI / BamHI restriction endonuclease site and the N-terminal 6 His amino acids (His-tag). The positive strand sequence is : GCG GGATCC ATG CAT CAC CAT CAC CAT CAC TTC ATC CTC ATC AGC TGT GGG GGA GCC CCA ACTCAG CCT CCA GGA CTC CGG CCT CAA ACC CAA TGA TCT AGA GCG, the reverse chain sequence is: CGC TCTAGA TCA TTG GGT TTG AGG CCG GAG TCC TGG AGG CTG AGT TGG GGC TCC CCC ACA GCTGAT GAG GAT GAA GTG ATG GTG ATG GTG ATG CAT GGA TCC CGC. The synthesized single chains were mixed in equal ...

Embodiment 2

[0043] Example 2, R9-M1-21 polypeptide chemical solid-phase synthesis process.

[0044] The R9-M1-21 polypeptide (RRR RRR RRR FIL ISC GGA PTQ PPGLRP QTQ) was synthesized by chemical solid-phase synthesis. Taking the synthesis of 10 mg product as an example, larger-scale synthesis can be scaled up according to standard processes.

[0045] 1. Main raw materials and reagents. Fmoc-Gln(Trt)-OH(glutamine), Fmoc-Thr(But)-OH(threonine), Fmoc-Pro-OH(proline), Fmoc-Arg(Pbf)-OH(arginine acid), Fmoc-Leu-OH (leucine), Fmoc-Gly-OH (glycine), Fmoc-Ala-OH (alanine), Fmoc-Cys(Trt)-OH (cysteine), Fmoc -Ser(Tbu)-OH(serine), Fmoc-Ile-OH(isoleucine), Fmoc-Phe-OH(phenylalanine), 2-Chlorotrityl Chloride Resin(2 chloro resin), DMF(N, N-dimethylformamide), DCM (dichloromethane), acetonitrile, HBTU (benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate), DIEA (N, N-diisopropylethylamine), TFA (trifluoroacetic acid), TIS (triisopropylsilane), EDT (1,2-ethanedithiol), ether, piperidine, eth...

Embodiment 3

[0065] Example 3, the R9-M1-21 polypeptide can effectively enter tumor cells.

[0066]Using the chemical solid-phase synthesis method described in Example 2, FITC fluorescent group-labeled R9-M1-21 polypeptide was synthesized and used to treat HEK293T tumor cells (50 μM). After 4 hours, wash with PBS and fix the cell samples with 4% formaldehyde. The distribution of the polypeptide in the cell was observed under a fluorescence microscope (400X), which confirmed that the FITC fluorescent group-labeled R9-M1-21 polypeptide can effectively penetrate the membrane and distribute in the cytoplasm and nucleus ( image 3 A).

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Abstract

The invention discloses a polypeptide derived from 21 amino acid residue sequences on 106-126 positions at a nitrogen terminal of the FOXM1 protein and a synthesis method of the polypeptide and provides a candidate for developing a polypeptide antitumor drug. A peptide fragment has a protein with one of the following amino acid residue sequences; 1) SEQ ID NO:1 in a sequence table; and 2) substituting, deleting, inserting and / or adding one, two or a plurality of amino acid residues in the SEQ ID NO:1 in the sequence table to achieve the polypeptide capable of inhibiting tumors. The polypeptidewith membrane penetrating capability, prepared from the amino acid sequence SEQ ID NO:1 in the sequence table, shows an effect on inhibiting various tumor cells.

Description

technical field [0001] The invention belongs to the fields of polypeptide medicine and oncology, and relates to the synthesis and application of an anti-tumor polypeptide derived from FOXM1 protein. Background technique [0002] From the gene expression analysis of various human tumor samples, it was found that the expression of transcription factor FOXM1 was increased in tumor cells, and the detection of its expression level has been used in the diagnosis and prognosis of various tumors (US7056674, 7081340, 7308364, 7526387, 7531300, CN201510355817 .5). From the perspective of gene function, FOXM1 was first identified as a protein regulating cell cycle and cell proliferation (Mol Cell Biol 1997. 17: 1626-1641). In the process of cell proliferation, FOXM1 is involved in regulating the transcription of multiple genes related to the cell cycle, thereby controlling the process of cell DNA replication and mitosis (Mol CellBiol 1999. 19: 8570-8580, Proc Natl Acad Sci US A 2002. ...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61K38/17A61P35/00C12N15/62C12N15/85
CPCA61K38/00C07K14/4748C07K2319/10
Inventor 谭拥军张振旺余景卫
Owner XINSHENG KANGYUAN BIOPHARML
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