A short peptide targeting SUV39H1 and its application in tumor treatment

Abstract

This invention provides a short peptide targeting SUV39H1 and its application in tumor treatment. The amino acid sequence of the short peptide is shown in SEQ ID NO: 1. The short peptide effectively blocks the interaction between PRMT1 and SUV39H1 by precisely targeting the PRMT1-SUV39H1 binding region, while simultaneously downregulating the methylation and protein levels of SUV39H1, achieving precise targeted intervention against SUV39H1. This invention provides a novel SUV39H1 intervention method that is precisely targeted, highly safe, and widely applicable, breaking through the current technical bottlenecks in tumor treatment.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and specifically relates to a short peptide targeting SUV39H1 and its application in the treatment of tumors. Background Technology

[0002] The development and progression of tumors is a complex process involving multiple factors and stages of abnormal regulation. Among these, epigenetic dysregulation has become one of the core research targets in the field of tumor therapy. Histone methylation, as a key mechanism of epigenetic regulation, is closely related to the proliferation, apoptosis resistance, and metastatic ability of tumor cells when its dynamic balance is disrupted. Histone methyltransferase SUV39H1, as the core enzyme regulating the trimethylation of lysine 9 of histone H3 (H3K9me3), plays a crucial role in maintaining the stability of heterochromatin structure and genome integrity. SUV39H1 promotes heterochromatin formation by catalyzing the deposition of H3K9me3. If its expression is lost or its function is abnormal, it will lead to heterochromatin disintegration, genomic instability, and accumulation of DNA damage, thereby inducing malignant transformation of cells.

[0003] Clinical studies and basic experiments have confirmed that SUV39H1 is dysregulated in various malignant tumors: in samples from patients with breast cancer, hepatocellular carcinoma, renal cell carcinoma, and colorectal cancer, the expression level of SUV39H1 is significantly higher than that in normal tissues, and its high expression is positively correlated with tumor stage progression, lymph node metastasis, and poor prognosis, suggesting that SUV39H1 may be a potential target for tumor therapy. Further mechanistic studies have shown that inhibiting SUV39H1 activity can activate endogenous retroviruses, thereby triggering the cGAS-STING innate immune signaling pathway, inducing the expression of downstream interferon-related genes, enhancing the body's anti-tumor immune response, and ultimately inhibiting tumor cell growth. This finding provides a clear theoretical basis for tumor therapy strategies targeting SUV39H1.

[0004] Currently, targeted interventions against SUV39H1 are limited to two small-molecule chemical inhibitors: chaetocin and F5446. While chaetocin, as a natural product inhibitor, can inhibit SUV39H1 activity, it has significant limitations: its target lacks specificity, simultaneously inhibiting not only SUV39H1 but also another histone methyltransferase G9a, SETDB1, and thioredoxin reductase (TrxR), leading to untargeted cytotoxicity and damage to normal cells during treatment, severely limiting its clinical translation. F5446, a newer selective SUV39H1 inhibitor, has only been validated in colorectal cancer models—studies have shown that it can reduce H3K9me3 deposition in the FAS promoter region, upregulate Fas expression, and enhance FasL-induced apoptosis in colon cancer cells. However, the therapeutic effects of this inhibitor on other common tumors such as breast cancer and lung cancer are still unclear, failing to meet the treatment needs of multiple tumor types.

[0005] In summary, existing small molecule inhibitors targeting SUV39H1 have key drawbacks such as insufficient specificity, high toxicity risk, or narrow anti-tumor spectrum. There is an urgent need to develop a novel SUV39H1 intervention method that is precise in targeting, safe, and widely applicable, in order to break through the current technical bottlenecks in cancer treatment. Summary of the Invention

[0006] To address the problems existing in the prior art, the present invention aims to provide a short peptide targeting SUV39H1 and its application in tumor treatment. This short peptide effectively blocks the interaction between PRMT1 and SUV39H1 by precisely targeting the PRMT1-SUV39H1 binding region, while simultaneously downregulating the methylation and protein levels of SUV39H1, thus achieving precise targeted intervention against SUV39H1.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] The first aspect of this invention provides a short peptide targeting SUV39H1, the amino acid sequence of which is shown in SEQ ID NO: 1, wherein SEQ ID NO: 1 is:

[0009] GRKKRRQRRRPQGGGSGCECQDCLWAPTGGCCPGASLHKFA.

[0010] Furthermore, the short peptide is prepared by a solid-phase polypeptide synthesis method.

[0011] Furthermore, the short peptide can bind to the PRMT1 protein and inhibit the interaction between PRMT1 and SUV39H1; the binding dissociation constant Kd of the short peptide to the PRMT1 protein is 100–300 nM.

[0012] The second aspect of the present invention provides the use of the short peptide targeting SUV39H1 described in the first aspect in the preparation of a medicament for treating tumors.

[0013] Furthermore, the tumor is a solid cancer including breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, and kidney cancer.

[0014] Furthermore, the application specifically binds to PRMT1 via a short peptide, blocking the interaction between PRMT1 and SUV39H1, while simultaneously downregulating the methylation and protein levels of SUV39H1.

[0015] A third aspect of the present invention provides an oncology pharmaceutical composition comprising the short peptide targeting SUV39H1 as described in the first aspect, and a pharmaceutically acceptable carrier or excipient.

[0016] Furthermore, the dosage form of the pharmaceutical composition is an injection.

[0017] Furthermore, the injection is administered via intraperitoneal injection at a dose of 10-20 mg / kg.

[0018] The TAT-SUV-peptide short peptide designed in this invention addresses the shortcomings of existing SUV39H1-targeted tumor therapy technologies and possesses the following core beneficial effects:

[0019] 1. Innovative Mechanism and Precise Targeting: This invention is the first to discover the interaction between PRMT1 and SUV39H1 and the tumor regulatory mechanism by which PRMT1 maintains the stability of SUV39H1. The TAT-SUV-peptide short peptide described in this application precisely targets the binding region between the two (the Glu180–Ala204 fragment of SUV39H1), specifically blocking the interaction and avoiding the non-specific inhibition of multiple targets by existing trachomatis. The intervention precision is superior to existing small molecule inhibitors.

[0020] 2. Excellent binding activity: Micro-thermophoresis experiments confirmed that the dissociation constant (Kd = 208 nM) of the short peptide TAT-SUV-peptide described in this application with PRMT1 is highly close to the binding affinity (Kd = 199.6 nM) of the full-length SUV39H1 and PRMT1; cell experiments showed that it can downregulate the methylation level of SUV39H1 in a concentration-dependent manner, and significantly reduce the amount of endogenous SUV39H1 protein after 72 hours, demonstrating excellent inhibitory efficiency;

[0021] 3. Broad-spectrum antitumor activity: The TAT-SUV-peptide short peptide described in this application can inhibit the proliferation and colony formation of breast cancer cells (MDA-MB-231) in vitro; it also has inhibitory effects on mouse orthotopic breast cancer (Py8119, 4T1 cells) and nude mouse lung cancer metastasis (A549-luci cells) in vivo (dose 10-25mg / kg, 3 times a week), making up for the shortcomings of the existing F5446 which only targets colorectal cancer and has a narrow antitumor spectrum;

[0022] 4. High safety: In animal experiments, the TAT-SUV-peptide short peptide described in this application had no effect on mouse body weight at therapeutic doses and showed no obvious toxicity, thus solving the problem of toxicity of chrysogenin to normal cells; moreover, it is prepared by solid-phase peptide synthesis, with controllable purity, combining safety and accessibility, which is conducive to clinical translation.

[0023] 5. Significant clinical value: The TAT-SUV-peptide short peptide described in this application can degrade SUV39H1 and downregulate H3K9me3, and has a dual effect of "direct tumor inhibition + activation of cGAS-STING immune signaling". It can delay the progression of breast cancer and other tumors, buy time for patients' subsequent comprehensive treatment, and is expected to improve prognosis. Attached Figure Description

[0024] The present invention will be further described below with reference to the accompanying drawings and embodiments:

[0025] Figure 1 : Conformation diagram of the SUV39H1 (blue)-PRMT1 (green) complex, in which SUV39H1-derived peptides are shown in purple, and a magnified view of hydrogen bonds at the interface of the two proteins is highlighted in red.

[0026] Figure 2 Figure 1 shows the results of molecular dynamics simulation analysis. In this figure, A represents the conformational overlap of the PRMT1 (green) and PRMT1 (blue)_SUV-peptide (purple) complexes, and B represents the root mean square deviation curves of PRMT1 and PRMT1_SUV-peptide in a 100-nanosecond molecular dynamics simulation.

[0027] Figure 3 : Immunoprecipitation (Co-IP) verification diagram showing that the 25aa peptide derived from SUV39H1 inhibits the binding of SUV39H1 to PRMT1 and downregulates its methylation level in cells;

[0028] Figure 4Figure 1 shows the effect of TAT-SUV-peptide treatment on the methylation level and protein stability of endogenous SUV39H1 in cells. In this figure, A is the effect of Co-IP assay on the binding of TAT-SUV-peptide to PRMT1-SUV39H1 and the methylation level of SUV39H1, and B is the effect of Western Blot assay on the protein level of SUV39H1.

[0029] Figure 5 : Inhibitory effect of TAT-SUV-peptide on breast cancer cell proliferation and colony formation, where A is the WST-1 proliferation assay and B is the colony formation assay;

[0030] Figure 6 Figure 1 shows in vivo experimental data on the inhibition of tumor growth and downregulation of SUV39H1 and H3K9me3 levels in tumor tissue by TAT-SUV-peptide in an orthotopic mouse model of breast cancer. A is a schematic diagram of the in vivo Py8119 cell experiment setup; B is an image of the primary tumor; C is the tumor growth curve; D is the tumor weight; E is the mouse body weight; F is a schematic diagram of the in vivo 4T1 cell experiment setup; G is an image of the primary tumor; H is the tumor growth curve; I is the tumor weight; J is the mouse body weight; and K is a Western blot experiment using two groups of mouse breast tumors.

[0031] Figure 7 : In vivo imaging experiment of TAT-SUV-peptide inhibiting the in vivo metastasis of lung cancer cells; where A is the in vivo imaging image and B is the trend of total flux change. Detailed Implementation

[0032] The embodiments described are provided to better illustrate the present invention, but are not intended to limit the scope of the invention to the embodiments described. Therefore, non-essential improvements and adjustments made to the embodiments by those skilled in the art based on the above description are still within the scope of protection of the present invention.

[0033] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0034] The present invention will be described in detail below through embodiments. It should be understood that the following embodiments are only used to exemplify and further explain and illustrate the content of the present invention, and are not intended to limit the present invention.

[0035] The reagents and materials used in the following embodiments of the present invention include: concentrated hydrochloric acid, concentrated sulfuric acid, sodium hydroxide, xylene, sodium bicarbonate, isopropanol, chloroform, glycerol, anhydrous ethanol, methanol, glacial acetic acid, glucose, anhydrous sodium acetate, calcium chloride, etc., purchased from Beijing Chemical Plant; hydroquinone, sodium 2-mercaptoethyl sulfonate, paraformaldehyde, chloroquine diphosphate, ammonium persulfate, diethyl pyrocarbonate (DEPC), crystal violet, Coomassie Brilliant Blue R250, magnesium chloride hexahydrate, manganese chloride, sodium chloride, boric acid, hydrogen... Sodium oxide, sodium dodecyl sulfate (SDS), tetramethylethylenediamine (TEMED), sodium deoxycholate, sodium nitroprusside, ethylenediaminetetraacetic acid (EDTA), sodium orthovanadate, HEPES, dimethyl sulfoxide (DMSO), sodium pentobarbital, dithiothreitol (DTT), β-mercaptoethanol, bromophenol blue, CHAPS, Tris, Tween-20, NP-40, Triton X-100, dNTP, chloramphenicol (Cam), etc., were purchased from Sigma.

[0036] Cell culture:

[0037] Human breast cancer cell line MDA-MB-231, human lung cancer cell line A549-luci, and mouse breast cancer cell lines 4T1 and Py8119 were all purchased from ATCC and cryopreserved in our laboratory. MDA-MB-231 cells were cultured in DMEM medium; A549-luci and 4T1 cells were cultured in RPMI 1640 medium; and Py8119 cells were cultured in Ham's F-12K medium. DMEM and RPMI 1640 complete medium contained 10% fetal bovine serum, while Ham's F-12K complete medium contained 5% fetal bovine serum. All cells were cultured in an incubator at 37°C and 5% CO2.

[0038] Example 1: Solid-phase synthesis and purification of TAT-SUV-peptide

[0039] This embodiment provides a short peptide (TAT-SUV-peptide) targeting SUV39H1. The amino acid sequence of the short peptide is shown in SEQ ID NO: 1, where SEQ ID NO: 1 is:

[0040] GRKKRRQRRRPQGGGSGCECQDCLWAPTGGCCPGASLHKFA.

[0041] The short peptide TAT-SUV-peptide described in this example comprises the membrane-penetrating peptide TAT (GRKKRRQRRRPQ), the linker (GGGS), and Glu180~Ala204 (GCECQDCLWAPTGGCCPGASLHKFA).

[0042] TAT-SUV-peptide was prepared using solid-phase peptide synthesis (SPPS), where amino acids are sequentially coupled to a resin to form a peptide chain. After sequence synthesis, the N-terminal Fmoc protecting group was deprotected (after N-terminal modification), followed by deprotection of the side chain protecting groups, allowing the peptide to be cleaved from the resin. The specific steps included:

[0043] 1. Synthesis steps:

[0044] (1) Resin pretreatment: Take 1g of Fmoc-Wang resin and add it to the synthesis reaction column. Soak it in DMF for 30min to activate the hydroxyl groups of the resin. Then filter to remove DMF.

[0045] (2) Fmoc deprotection: Add 20% Pip / DMF solution (v / v) to the reaction column, shake at room temperature for 20 min, filter to remove the solution; wash the resin with DMF 5 times (5 min each time), dry it and take a small amount of resin for ninhydrin detection (reagent A: 0.2% ninhydrin ethanol solution; reagent B: 5% pyrrole ethanol solution). The resin turns blue, confirming that the Fmoc protecting group has been completely removed.

[0046] (3) First amino acid coupling: Dissolve 1.5 eq Fmoc-Ala-OH (the first amino acid at the C-terminus of the short peptide), 1.5 eq HBTU, and 1.5 eq HOBt in DMF, add 3 eq DIPEA to adjust the pH to 8.0, mix well, add to the reaction column, and shake at room temperature for 4 h; filter to remove the reaction solution, wash the resin 3 times with DMF, and the ninhydrin test is colorless, confirming complete coupling.

[0047] (4) Repeated synthesis cycle: The “Fmoc deprotection-amino acid coupling-washing-detection” steps were repeated from the C-terminus to the N-terminus of the short peptide sequence. Each coupling used 1.5 eq Fmoc-protected amino acid, 1.5 eq HBTU, 1.5 eq HOBt and 3 eq DIPEA to ensure efficient coupling of each amino acid.

[0048] (5) Peptide cleavage and deprotection: After synthesis, cleavage buffer was added to the reaction column, and the column was shaken at room temperature for 2 hours. The cleavage buffer was collected. The resin was washed twice with a small amount of TFA. The cleavage buffers were combined and 10 times the volume of pre-cooled diethyl ether was added to precipitate the crude peptide. The column was allowed to stand at 4°C for 30 minutes, centrifuged at 12,000 rpm for 10 minutes, and the supernatant was discarded. The precipitate was washed three times with diethyl ether and dried under vacuum to obtain crude TAT-SUV-peptide powder.

[0049] 2. Purification steps:

[0050] (1) Crude peptide dissolution: Take 100 mg of crude peptide, dissolve it by sonication with 0.1% TFA aqueous solution (containing 5% acetonitrile), and filter it through a 0.22 μm filter membrane.

[0051] (2) HPLC purification conditions: The chromatographic column was an Agilent Zorbax SB-C18 (4.6×250mm, 5μm); mobile phase A: 0.1% TFA aqueous solution, mobile phase B: 0.1% TFA acetonitrile solution; elution gradient: 0-5min 5% B, 5-30min 5%-35% B, 30-35min 35%-95% B; flow rate 1mL / min, detection wavelength 220nm.

[0052] (3) Fraction collection and verification: Collect the main peak fraction with consistent retention time, and detect the molecular weight using MALDI-TOF-MS; detect the purity using HPLC, collect the fraction with a purity ≥95%, and freeze-dry to obtain pure TAT-SUV-peptide.

[0053] Example 2: Verification of the binding activity of TAT-SUV-peptide to PRMT1

[0054] This embodiment aims to explore the interaction mechanism between the protein arginine methyltransferase PRMT1 and the histone methyltransferase SUV39H1. This embodiment includes GST pull-down experiments, molecular docking, and molecular dynamics simulations.

[0055] GST pull-down assay: Purified GST or GST fusion protein was incubated with glutathione-agarose gel 4B beads for 4 hours. The supernatant was then discarded by centrifugation. The 4B beads were further incubated with the His fusion protein overnight at 4°C, and washed three times with pre-cooled BC100 before Western blot analysis.

[0056] Experiments revealed that glutamic acid residues from position 180 to alanine residue 204 of SUV39H1 can interact with PRMT1. Specifically, four amino acid residues in SUV39H1—Gln184, Trp188, Gly192, and Lys202—play a crucial role in the SUV39H1-PRMT1 binding process. Figure 1 ).

[0057] Molecular dynamics simulations show that the binding of the SUV39H1-derived peptide to PRMT1 does not affect the conformation of PRMT1. Figure 2First, this embodiment constructed a eukaryotic expression plasmid expressing a 25-amino acid peptide derived from SUV39H1 (Glu180–Ala204:GCECQDCLWAPTGGCCPGASLHKFA). Subsequently, at the cellular level, it was verified that the 25-amino acid peptide could inhibit the binding of SUV39H1 to PRMT1 and downregulate the methylation level of SUV39H1. Figure 3 ).

[0058] Furthermore, the short peptide TAT-SUV-peptide described in Example 1 was designed, and a micro-thermophoretic experiment was conducted:

[0059] His-PRMT1 was dialyzed. Then, His-PRMT1 was fluorescently labeled using the RED-NHS protein labeling kit according to a standard protocol. TAT-SUV-peptide was diluted to 16 gradients using MST-optimized buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, 10 mM MgCl2, 0.05% Tween 20). The constant concentration of fluorescently labeled protein was then mixed with equal volumes of the gradient dilutions and incubated at room temperature in the dark for 15 minutes. The mixture was then adsorbed via capillary action, and the dissociation constant (Kd) was measured using the instrument. The Kd value was determined using Nano Temper analysis software.

[0060] It was determined that TAT-SUV-peptide can directly bind to PRMT1 with a Kd value of 208 nM. This value is very close to the Kd value (199.6 nM) of the full-length SUV39H1 binding to PRMT1, and there is no significant difference between the two (P>0.05). This proves that TAT-SUV-peptide can bind to PRMT1 efficiently. Furthermore, the specific binding of TAT-SUV-peptide to PRMT1 does not change the overall spatial conformation of PRMT1, further demonstrating the targeting of short peptides and avoiding functional abnormalities of other target proteins of PRMT1 caused by conformational changes.

[0061] Example 3: Verification of the effect of TAT-SUV-peptide on breast cancer cells

[0062] This embodiment uses the purified short peptide TAT-SUV-peptide from Example 1 to treat MDA-MB-231 breast cancer cells, investigating the effects of the short peptide on PRMT1-SUV39H1 binding and protein levels, as well as its effects on breast cancer cell proliferation and colony formation. Specifically:

[0063] 1. Effects of short peptides on PRMT1-SUV39H1 binding and protein levels

[0064] (1) Cell treatment: MDA-MB-231 cells were seeded in 6-well plates (2×10⁶ cells / wells). 5 After culturing for 24 hours, 0, 10, and 20 μM TAT-SUV-peptide were added respectively, and the cells were cultured for another 72 hours.

[0065] (2) Immunoprecipitation (IP): 7 μl of anti-Flag M2 beads were added to the supernatant of the cell lysate after centrifugation and incubated overnight at 4°C. The next day, the M2 beads were washed three times with RIPA buffer and then boiled at 100°C for 5 minutes with loading buffer. Western blot experiments were then performed.

[0066] (3) Western blot analysis: Cells were washed once with pre-chilled PBS and lysed using RIPA lysis buffer containing protease inhibitors. After lysis, the supernatant was collected by centrifugation. The sample with loading buffer was heated at 100°C for 5 minutes and separated by SDS-PAGE. The PVDF membrane was immunoblotted overnight with primary antibody at 4°C. After washing with TBST buffer, the membrane was incubated with secondary antibody at room temperature for 1 hour. Chemiluminescence of the target band was detected using ECL.

[0067] 2. Cell proliferation and plate cloning

[0068] (1) For cell proliferation assays, cells were seeded into 96-well plates at a density of 1000 cells / well. TAT-SUV-peptide was used at the concentration specified in the cell treatment section above. Cells were treated with WST-1 (10 μl / well) at 37°C for 2 hours. The absorbance was then measured at 450 nm using a microplate reader.

[0069] (2) For the plate cloning experiment, 1000 cells were seeded into 6-well plates. Two weeks later, the cells were fixed, stained with crystal violet, and photographed.

[0070] TAT-SUV-peptide was found to inhibit the binding of SUV39H1 and PRMT1 in a concentration-dependent manner and to downregulate the methylation level of SUV39H1. Figure 4 (A)

[0071] like Figure 4 As shown in Figure B, after 72 hours of treatment with TAT-SUV-peptide, the level of endogenous SUV39H1 began to decrease significantly.

[0072] Furthermore, this embodiment evaluated the effect of TAT-SUV-peptide on breast cancer cell growth. For example... Figure 5The results show that TAT-SUV-peptide significantly inhibited the proliferation and colony formation of cancer cells.

[0073] Example 4: Inhibitory effect of TAT-SUV-peptide on the growth of orthotopic breast cancer in mice

[0074] In this embodiment, C57BL / 6-Py8119 animal model and BALB / c-4T1 model were constructed respectively.

[0075] C57BL / 6-Py8119 model: Py8119 cells in logarithmic growth phase were collected and the concentration was adjusted to 1×10⁻⁶ with PBS. 6 10 mice were injected in situ into the fourth pair of mammary fat pads on the right side. On the third day after inoculation, the mice were randomly divided into two groups (n=5) according to tumor volume (V=length×width2 / 2): control group (PBS) and treatment group (20mg / kg TAT-SUV-peptide). The mice were injected intraperitoneally three times a week for a total of eight times.

[0076] BALB / c-4T1 model: 4T1 cells were seeded using the same method (1×10⁻⁶). 6 (cells / 100μL), grouped in the same way as the Py8119 model.

[0077] We found that TAT-SUV-peptide significantly inhibited the growth of breast tumors in mice without affecting their body weight, indicating that TAT-SUV-peptide has low toxicity at the administered dose. Next, we extracted total protein and histones from mouse tumors for analysis. The results showed that TAT-SUV-peptide reduced the expression of SUV39H1 and the level of H3K9me3 in mouse tumors. Figure 6 ).

[0078] Example 5: Inhibitory effect of TAT-SUV-peptide on lung cancer cell metastasis

[0079] This embodiment establishes a lung cancer metastasis model: Log-phase A549-luci lung cancer cells were collected and their concentration was adjusted to 5 × 10⁻⁶ PBS. 5 Cells / 50μL; After anesthetizing nude mice, cancer cells were injected into the nude mice via the left ventricle intracardiac injection, a total of 10 mice; On the 7th day after inoculation, the tumor burden was detected by in vivo imaging (intraperitoneal injection of D-fluorescein potassium salt, 150mg / kg, imaging 10min later). The mice were randomly divided into a control group (PBS) and a treatment group (20mg / kg TAT-SUV-peptide) according to the number of photons, with 5 mice in each group. The mice were given the drug 3 times a week for a total of 9 times.

[0080] like Figure 7As shown, in vivo imaging of small animals was performed on days 14, 17, and 21 after injection of lung cancer cells. We found that TAT-SUV-peptide significantly inhibited systemic metastasis of lung cancer cells without affecting the body weight of mice.

[0081] Finally, it should be noted that the above description is only used to illustrate the technical solutions of the present invention and is not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention.

Claims

1. A short peptide targeting SUV39H1, characterized in that, The amino acid sequence of the short peptide is shown in SEQ ID NO: 1, where SEQ ID NO: 1 is: GRKKRRQRRRPQGGGSGCECQDCLWAPTGGCCPGASLHKFA.

2. The short peptide targeting SUV39H1 according to claim 1, characterized in that, The short peptide was prepared by solid-phase polypeptide synthesis.

3. The short peptide targeting SUV39H1 according to claim 1 or 2, characterized in that, The short peptide can bind to the PRMT1 protein and inhibit the interaction between PRMT1 and SUV39H1; the binding dissociation constant Kd of the short peptide to the PRMT1 protein is 100–300 nM.

4. The use of the short peptide targeting SUV39H1 as described in any one of claims 1 to 3 in the preparation of a medicament for treating tumors, characterized in that, The tumor is either breast cancer or lung cancer.

5. The application according to claim 4, characterized in that, The application specifically binds to PRMT1 via a short peptide, blocking the interaction between PRMT1 and SUV39H1, while simultaneously downregulating the methylation and protein levels of SUV39H1.

6. A tumor drug composition, characterized in that, It comprises a short peptide targeting SUV39H1 as described in any one of claims 1 to 3, and a pharmaceutically acceptable carrier or excipient.

7. The tumor drug composition according to claim 6, characterized in that, The dosage form of the pharmaceutical composition is an injection.

8. The tumor drug composition according to claim 7, characterized in that, The injection is administered via intraperitoneal injection at a dose of 10-20 mg / kg.

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