CN113214361B - Stress particle inhibitor containing FGDF motif and application thereof - Google Patents
Stress particle inhibitor containing FGDF motif and application thereof Download PDFInfo
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
Abstract
The invention designs a stress particle (SGs) inhibitor containing FGDF motif, which promotes the depolymerization of SGs by combining with G3BP1/2, thereby inhibiting the generation of stress particles and further treating diseases related to the generation of SGs, such as tumors or neurodegenerative diseases.
Description
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to active peptides containing FGDF motifs, which can be combined with G3BP1/2 to promote depolymerization of stress particles, thereby inhibiting generation of the stress particles and generating corresponding biological effects.
Background
There are many membrane-free structures in cells that are rich in RNA and protein, called Ribonucleoproteins (RNPs). These RNP particles are independent organelles composed of thousands of molecules, ubiquitous in cells. Eukaryotic cells form aggregated granular mRNA-protein complexes, i.e., Stress Granules (SGs), in the cytoplasm in response to stress stimuli such as endoplasmic reticulum stress, heat shock, hypoxia, and arsenate.
The formation of SGs has important physiological significance, including minimizing damage to cells caused by stress by regulating mRNA translation and inhibiting apoptosis-related signaling pathways, and promoting adaptation and survival of cells under stress conditions. Research shows that SGs are closely related to the occurrence of various diseases, including various tumors, neurodegenerative diseases, virus infection-related diseases and the like. Tumor cells promote survival under stress conditions by using SGs to participate in the development of tumor drug resistance, and the formation of protein aggregates in some neurodegenerative diseases is also closely related to abnormal SGs.
Ubiquitin-specific protease 10 (USP 10) is an important member of the deubiquitinating enzymes (DUBs) family. USP10 is involved in the regulation of various vital activities in cells, such as cell proliferation, apoptosis, DNA damage repair, inflammatory responses, etc. Meanwhile, USP10 shows an important role in the occurrence and development processes of various tumors. Studies have shown that the protein USP10 inhibits the assembly of SGs by binding to G3BP1, and is associated with the conserved FGDF motif in its gene sequence. In addition, some viral genes encode proteins, such as the Semliki forest virus nsp3 protein, that also contain the FGDF motif and also inhibit SGs assembly in a similar manner. Further studies have shown that the above-mentioned SGs-inhibiting activity depends on the FGDF motif leader sequence and successor sequences in addition to the FGDF motif, but the FGDF motif has no deep study as to what kind of association exists between the FGDF motif leader sequence and successor sequences. Although there is increasing interest in developing new active agents comprising the FGDF motif for the treatment of SGs-related diseases, there is currently no breakthrough progress.
Disclosure of Invention
Based on the research of FGDF motif and SGs inhibition in the prior art, the invention researches the USP10 containing FGDF motif and nsp3 protein of Semliki Forest Virus (SFV), and obtains an active fragment containing FGDF motif by using a gene truncation method.
The specific technical scheme of the invention is as follows:
a class of active peptides comprising the FGDF motif having the amino acid sequence of SEQ ID No: 1-3.
Another object of the present invention is to provide a gene expressing the active peptide of the present invention.
Another object of the present invention is to provide a gene expressing an active peptide derived from Caprin 1.
Specifically, the gene sequence is shown as SEQ ID No: 4-6.
Another object of the present invention is to provide the use of the active peptide comprising FGDF motif or the gene expressing the active peptide comprising FGDF motif of the present invention for preparing stress particle inhibitors.
Preferably, the stress particle inhibitor is a drug for treating diseases associated with SGs production.
Such diseases include, but are not limited to, tumors or neurodegenerative diseases.
The tumors include, but are not limited to, head and neck cancer, lung cancer, prostate cancer, colon cancer, breast cancer, melanoma, osteosarcoma, liver cancer, stomach cancer, rectal cancer, kidney cancer, bladder cancer, endometrial cancer, cervical cancer, testicular cancer and the like.
Further, the tumor is a tumor which generates drug resistance to an antitumor drug. The antitumor drug can be Oxaliplatin (Oxaliplatin), Bortezomib (Bortezomib), 5-fluorouracil (5-FU), Docetaxel (Docetaxel), Cabazitaxel (Cabazitaxel), Sorafenib (Sorafenib) and the like.
The neurodegenerative diseases include acute neurodegenerative diseases and chronic neurodegenerative diseases, the former mainly including but not limited to Cerebral Ischemia (CI), cerebral injury (BI), epilepsy; the latter mainly include, but are not limited to, Amyotrophic Lateral Sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), and the like.
The active peptide or the gene of the active peptide or the carrier expressing the gene of the active peptide can be used as an active ingredient to prepare medicaments.
The vector may be an expression plasmid or a viral vector, such as a prokaryotic expression vector, a eukaryotic expression vector, an adenoviral expression vector, a lentiviral expression vector, and the like.
Preferably, the vector is selected from mammalian expression plasmids such as pCS2, pcDNA3, pCMV, pTRE, pMEP4, pCGN, pCAGGS, etc., or adenoviral, lentiviral expression vectors such as pDC316, pDC311, pDC312, or pDC 315.
Preferably, the drug is a drug delivery vehicle or delivery system, such as a liposome, nanomaterial, or the like, that can carry a membrane-penetrating drug delivery vehicle or delivery system that facilitates the penetration of the active peptide comprising the FGDF motif or the expression of the gene cell of the active peptide comprising the FGDF motif.
Alternatively, it is preferable that the active peptide containing the FGDF motif is coupled with a membrane penetration promoting substance or that the active peptide containing the FGDF motif is co-expressed with a co-expression vector of a cell-penetrating peptide or that the active peptide containing the FGDF motif is expressed using an expression vector having membrane penetration ability.
Another object of the present invention is to provide an active peptide comprising FGDF motif coupled to a penetrating peptide comprising (1) cationic peptide such as trans-activator of transcription TAT (YGRKKRRQRRR, HIV-1TAT Protein), drosophila homeotic transcription factor ANTP, VP22, lactoferricin hLF, poly-arginine oligomer R5, R6, R7, R8, R9 or polylysine, nuclear localization signal sequences (NLSs), such as mono-type NLSs (pkkkrkv), bi-type NLSs (krpaatkkagkkkkkkkkkk); antimicrobial peptides (AMPs), such as antimicrobial peptides LL-37, S413-PV, TP10, Buforin 2, etc.; (2) amphiphilic peptides, such as Model Amphiphilic Peptides (MAP), MPG, pentatin, transportan, CADY, C6M1, vascular endothelial-cadherin (pVEC), ARF (1-22), BPrPr, aromatic arrowhead peptides (sweet arrow peptide, SAP, VRLPPP); (3) hydrophobic peptides such as signal sequence VTVLALGALAGVGVG found in integrin beta 3, kaposi's fibroblast growth factor (AAVALLPAVLLALLAP).
The cell-penetrating peptide is linked to the N-terminus or C-terminus of an active peptide comprising the FGDF motif, either directly or through a linker peptide.
Preferably, the connecting peptide refers to a flexible peptide with 1-50 amino acid residues rich in Gly and/or Ala and/or Ser.
In a specific example, the cell-penetrating peptide is selected from drosophila homeotic transcription factor ANTP, and the amino acid sequence is shown in SEQ ID No: shown at 7.
In a specific example, the amino acid sequence of the active peptide comprising the FGDF motif coupled to the cell-penetrating peptide is shown in SEQ ID No: 8-10.
The invention has the advantages that:
1. the present invention successfully screens three polypeptide SGs inhibitors that contain the FGDF motif. The present invention shortens the 40 amino acid segment of USP10 protein containing 1-40 of FGDF motif to USP10(5-21) containing only 17 amino acids and is named hUSP 10-FGDF. And the nsp3 protein of SFV containing two FGDF motifs was separated and shortened and named nsp3-FGDF1 and nsp3-FGDF2, respectively. The results of immunofluorescence experiments show that over-expression of hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 inhibits SGs formation compared with the control group.
2. The invention couples hUSP10-FGDF with cell-penetrating peptide ANTP, which is named as SIP-U1. The experimental result shows that SIP-U1 can effectively inhibit Sorafenib-induced SGs and promote Sorafenib-induced apoptosis in HeLa cells. The active peptide containing the FGDF motif can be used for treating drug-resistant tumors.
Drawings
FIG. 1 shows the results of immunofluorescence experiments in which hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 inhibit SGs activity.
FIG. 2 shows the results of immunofluorescence experiments of hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 inhibiting SGs formed by the induction of the antitumor drug Sorafenib.
FIG. 3 shows the results of immunofluorescence experiment of hUSP10-FGDF coupled with cell-penetrating peptide for inhibiting SGs formed by the antitumor drug Sorafenib induction.
FIG. 4 shows the apoptosis-inducing activity of hUSP10-FGDF coupled to cell-penetrating peptide.
Detailed Description
The following examples illustrate specific steps of the present invention, but are not intended to limit the invention.
Terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art, unless otherwise specified. The present invention is described in further detail below with reference to specific examples and with reference to the data.
It will be understood that these examples are intended to illustrate the invention and are not intended to limit the scope of the invention in any way. In the following examples, various procedures and methods not described in detail are conventional methods well known in the art.
EXAMPLE 1 preparation of active peptides of the invention comprising the FGDF motif
The present invention shortens the 40 amino acid segment of USP10(1-40) containing the FGDF motif to USP10(5-21) containing only 17 amino acids, which was named hUSP10-FGDF (SEQ ID No: 1). The nsp3 protein containing two FGDF motifs was split and shortened and named nsp3-FGDF1(SEQ ID No: 2), nsp3-FGDF2(SEQ ID No: 3), respectively.
Constructing expression plasmids of hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2, and designing and synthesizing the following primers:
hUSP10-FGDF:
hUSP10-FGDF-F：5’-agcccgcagtatatttttggagattttagccctgatgaattcaatcaattct-3’(SEQ ID No：11)；
hUSP10-FGDF-R：5’-ctagagaattgattgaattcatcagggctaaaatctccaaaaatatactgcgggct-3’(SEQ ID No：12)；
nsp3-FGDF1：
nsP3-FGDF1-F：5’-aagctgcctttgacgttcggcgactttgacgagcacgaggtcgatgcgttgt-3’(SEQ ID No：13)；
nsP3-FGDF1-R：5’-ctagacaacgcatcgacctcgtgctcgtcaaagtcgccgaacgtcaaaggcagctt-3’(SEQ ID No：14)；
nsp3-FGDF2：
nsP3-FGDF2-F：5’-gcctccgggattactttcggagacttcgacgacgtcctgcgactaggccgct-3’(SEQ ID No：15)；
nsP3-FGDF2-R：5’-ctagagcggcctagtcgcaggacgtcgtcgaagtctccgaaagtaatcccggaggc-3’(SEQ ID No：16)。
with reference to molecular cloning, A laboratory Manual (fourth edition), Cold spring harbor laboratory Press/scientific Press, the above-mentioned paired primers (hUSP10-FGDF-F and hUSP10-FGDF-R, nsP3-FGDF1-F and nsP3-FGDF1-R, nsP3-FGDF2-F and nsP3-FGDF2-R) were annealed, respectively. The annealing step is as follows: taking 10. mu.M of each of the primer F and the primer R10. mu.l, adding d2H2O30 mul, mixing well, placing in a PCR instrument, setting the program to 95 ℃ for 5min, and then reducing the temperature by 0.5 ℃ every 5min until the temperature reaches 25 ℃. The annealed double-stranded primers were cloned into pCS2-GFP-Myc vector (Addgene, #15681) and sequenced by Biotech, Inc., Beijing Okagaku. The sequencing results showed correct.
Example 2 examination of inhibitory activity of hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 against SGs HeLa cell lines were inoculated in 6-well plates, and the plasmids expressing hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 constructed in example 1 were transfected into HeLa cells respectively and overexpressed in the cells when the confluency of the cells reached about 60%. When the confluency of cells reached about 80%, 12mL of the cell culture medium was taken and added to 12 μ L of 0.5mM AS in a 15mL centrifuge tube, mixed well, and the medium in a 6-well plate was replaced to stimulate the formation of SGs by HeLa cells (using endogenous G3BP1 AS a marker for SGs). Placing into carbon dioxide cell incubator, and culturing for 45 min. And taking out the 6-well plate for immunofluorescence experiment.
The results are shown in fig. 1, and indicate that overexpression of hhsp 10-FGDF inhibited SGs induced by AS compared to the control group (fig. 1A). Overexpression of nsp3-FGDF1 and nsp3-FGDF2 inhibited SGs induced by AS (FIG. 1B).
Example 3hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 inhibits the formation of SGs induced by the antitumor drug Sorafenib
HeLa cell lines were seeded in 6-well plates, and when the confluency of cells reached about 60%, HeLa cells were transfected with the plasmids expressing hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2, respectively, and overexpressed in the cells. When the cell confluence reached around 80%, 12mL of cell culture medium was taken in a 15mL centrifuge tube and HeLa cells were treated with 50 μ M Sorafenib to stimulate them to form SGs (endogenous G3BP1 was used as a marker for SGs). Through immunofluorescence experiments, it is found that over-expression of hUSP10-FGDF, nsp3-FGDF1 and nsp3-FGDF2 inhibits SGs induced by the antitumor drug Sorafenib compared with the control group (FIG. 2).
Example 4 inhibition of hUSP10-FGDF coupled with cell-penetrating peptide SGs induced by the antineoplastic agent Sorafenib hUSP10-FGDF was coupled with cell-penetrating peptide ANTP, named SIP-U1. Nsp3-FGDF1 was coupled to the cell-penetrating peptide ANTP, designated SIP-N1. Nsp3-FGDF2 was coupled to the cell-penetrating peptide ANTP, designated SIP-N2. The above-mentioned polypeptide fragments were synthesized by Shanghai Jier Biochemical company.
The HeLa cell line was seeded in 6-well plates, and when the confluency of cells reached about 80%, the medium was discarded, 1.2mL of the cell culture medium was added, along with 300. mu.L of 1mM TAT (negative control), SIP-U1, and the cells were placed in a carbon dioxide cell incubator and cultured for 2 h. The 6-well plate is taken out, prepared 15 mu L of 5mM Sorafenib is added into each well, and the well is put into a carbon dioxide cell incubator to be continuously cultured for 1.5h for carrying out immunofluorescence experiments. The results are shown in FIG. 3.
The results showed that SIP-U1 at a concentration of 200. mu.M was effective in inhibiting SGs induced by 50. mu.M Sorafenib in HeLa cells, compared to the control Sorafenib group, Sorafenib and TAT combination group.
Example 5 Activity of SIP-U1 to induce apoptosis
The HeLa cell line was inoculated into a 6-well plate, and when the confluency of cells reached about 95%, the medium was discarded, and the cells were treated by adding a medium containing TAT and SIP-U1 at a concentration of 200. mu.M, respectively, and cultured in a carbon dioxide cell incubator for 2 hours. Taking out the 6-pore plate, adding prepared 15 mu L of 5mM Sorafenib into each pore, putting into a carbon dioxide cell incubator for continuous culture for 1.5h, taking out the 6-pore plate, discarding the culture medium, adding 1mL of 4.5 mu M PI staining solution into each pore, putting into the carbon dioxide cell incubator for staining for 15min, observing under an inverted microscope, taking a picture, counting apoptotic cells, and performing data statistics. The results are shown in FIG. 4.
PI staining results are shown in fig. 4A, and apoptotic cell count statistics are shown in fig. 4B. The results show that compared with the control group of Sorafenib, the group of Sorafenib and TAT, the SIP-U1 can effectively enhance the sensitivity of HeLa cells to Sorafenib and promote Sorafenib-induced apoptosis.
Sequence listing
<110> Zhejiang university
<120> SGs inhibitors containing FGDF motif and application thereof
<160> 16
<170> SIPOSequenceListing 1.0
<210> 1
<211> 17
<212> PRT
<213> human
<400> 1
Ser Pro Gln Tyr Ile Phe Gly Asp Phe Ser Pro Asp Glu Phe Asn Gln
1 5 10 15
Phe
<210> 2
<211> 16
<212> PRT
<213> Semliki forest
<400> 2
Leu Pro Leu Thr Phe Gly Asp Phe Asp Glu His Glu Val Asp Ala Leu
1 5 10 15
<210> 3
<211> 17
<212> PRT
<213> Semliki forest
<400> 3
Ala Ser Gly Ile Thr Phe Gly Asp Phe Asp Asp Val Leu Arg Leu Gly
1 5 10 15
Arg
<210> 4
<211> 51
<212> DNA
<213> human
<400> 4
agcccgcagt atatttttgg agattttagc cctgatgaat tcaatcaatt c 51
<210> 5
<211> 48
<212> DNA
<213> Semliki forest
<400> 5
ctgcctttga cgttcggcga ctttgacgag cacgaggtcg atgcgttg 48
<210> 6
<211> 51
<212> DNA
<213> Semliki forest
<400> 6
gcctccggga ttactttcgg agacttcgac gacgtcctgc gactaggccg c 51
<210> 7
<211> 16
<212> PRT
<213> Drosophila
<400> 7
Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
1 5 10 15
<210> 8
<211> 33
<212> PRT
<213> Artificial Sequence
<400> 8
Ser Pro Gln Tyr Ile Phe Gly Asp Phe Ser Pro Asp Glu Phe Asn Gln
1 5 10 15
Phe Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys
20 25 30
Lys
<210> 9
<211> 32
<212> PRT
<213> Artificial Sequence
<400> 9
Leu Pro Leu Thr Phe Gly Asp Phe Asp Glu His Glu Val Asp Ala Leu
1 5 10 15
Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
20 25 30
<210> 10
<211> 33
<212> PRT
<213> Artificial Sequence
<400> 10
Ala Ser Gly Ile Thr Phe Gly Asp Phe Asp Asp Val Leu Arg Leu Gly
1 5 10 15
Arg Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys
20 25 30
Lys
<210> 11
<211> 52
<212> DNA
<213> Artificial Sequence
<400> 11
agcccgcagt atatttttgg agattttagc cctgatgaat tcaatcaatt ct 52
<210> 12
<211> 56
<212> DNA
<213> Artificial Sequence
<400> 12
ctagagaatt gattgaattc atcagggcta aaatctccaa aaatatactg cgggct 56
<210> 13
<211> 52
<212> DNA
<213> Artificial Sequence
<400> 13
aagctgcctt tgacgttcgg cgactttgac gagcacgagg tcgatgcgtt gt 52
<210> 14
<211> 56
<212> DNA
<213> Artificial Sequence
<400> 14
ctagacaacg catcgacctc gtgctcgtca aagtcgccga acgtcaaagg cagctt 56
<210> 15
<211> 52
<212> DNA
<213> Artificial Sequence
<400> 15
gcctccggga ttactttcgg agacttcgac gacgtcctgc gactaggccg ct 52
<210> 16
<211> 56
<212> DNA
<213> Artificial Sequence
<400> 16
ctagagcggc ctagtcgcag gacgtcgtcg aagtctccga aagtaatccc ggaggc 56
Claims (10)
1. Active peptides comprising the FGDF motif, characterized by an amino acid sequence as set forth in SEQ ID No: 1 to 3.
2. A nucleotide encoding the active peptide of claim 1.
3. The nucleotide according to claim 2, characterized in that the sequence is as shown in SEQ ID No: 4-6.
4. An active peptide comprising an FGDF motif coupled to a membrane-penetrating peptide, characterized in that the membrane-penetrating peptide is linked directly or via a linker peptide to the N-terminus or C-terminus of the active peptide comprising an FGDF motif of claim 1.
5. Active peptide according to claim 4, characterized in that the membrane-penetrating peptide is selected from the group consisting of the transcriptional transactivator TAT of the human immunodeficiency virus HIV, the drosophila homeotic transcription factor ANTP, VP22, lactoferrin peptide hLF, polyarginine oligomer R5, R6, R7, R8, R9, polylysine, the nuclear localization signal sequence peptide, the antimicrobial peptide LL-37, S413-PV, TP10, Buforin 2, the model amphipathic peptide MAP, MPG, pentratin, transportan, CADY, C6M1, vascular endothelial-cadherin pVEC, ARF, BPrPr, the aromatic arrowhead peptide SAP, the signal sequence found from integrin beta 3 or the Kaposi fibroblast growth factor.
6. The active peptide of claim 5, characterized by an amino acid sequence as set forth in SEQ ID No: 7-9.
7. An active peptide comprising an FGDF motif according to claim 1, a nucleotide according to claim 2 or 3, or a nucleotide sequence of SEQ ID No: 8, and the active peptide containing the FGDF motif and coupled with the cell-penetrating peptide is applied to preparing stress particle inhibitors.
8. The use according to claim 7, characterized in that the stress particle inhibitor is a medicament for the treatment of tumors, said tumors being endometrial or cervical cancer.
9. The use according to claim 8, wherein said tumor is resistant to an anti-tumor agent.
10. The use according to claim 9, characterized in that the antineoplastic drug is selected from one or more of oxaliplatin, bortezomib, 5-fluorouracil, docetaxel, cabazitaxel, sorafenib.
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| Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation;Panas MD等;《PLoS Pathogens》;20150206;第11卷(第02期);e1004659 * |
| 应激颗粒抑制剂的研究进展;李娟等;《生物医学》;20210409;第11卷(第02期);40-48 * |
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