CN107778367B - Polypeptide, application thereof and medicine containing polypeptide - Google Patents
Polypeptide, application thereof and medicine containing polypeptide Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1021—Tetrapeptides with the first amino acid being acidic
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C07K2319/00—Fusion polypeptide
Abstract
The invention provides a polypeptide, application thereof and a medicament containing the polypeptide, wherein the polypeptide can perform two-step self-assembly in series through the action of ALP and GSH to construct a nano material. The sequence of the polypeptide is NBD-GFFpYsserGD, wherein pY represents phosphorylated tyrosine, and ss represents a disulfide bond. The polypeptide can initiate a series two-step self-assembly process under the action of ALP and GSH to obtain a nano material; the simultaneous high expression of the liver cancer cells to extracellular ALP and intracellular GSH enables the polypeptide to show the strongest selectivity to the polypeptide, and can form nano-fibers in the liver cancer cells and inhibit the growth of the liver cancer cells.
Description
Technical Field
The invention relates to a polypeptide, application thereof and a medicament containing the polypeptide.
Background
The self-assembly process is an important tool for the preparation of supramolecular materials. Under the action of non-covalent bonds (e.g., hydrogen bonding, hydrophobic interactions, pi-pi stacking, and electrostatic interactions), self-assembled units spontaneously and progressively assemble into a functional material. Common methods include chemical triggering, external energy, heating and cooling, etc., while in the biological field biocatalysis can make self-assembled units more controllable and efficient. Today, catalytic self-assembly has been widely used in the construction of dynamically dispersed and reversible nanostructures. These nanostructures not only provide a platform for understanding the stepwise self-assembly process in biological systems, but also facilitate the use of nanomaterials in sensing, drug delivery, cell fate control, immunological manipulation, and regenerative medicine. However, most research methods focus mainly on using simple enzymes or small molecules (e.g. vitamin C or glutathione) to trigger the self-assembly process through a single step reaction. While single-step self-assembly results have shown the expected effect, multi-step self-assembly provides more complex and functional materials.
Disclosure of Invention
Object of the Invention
The inventor finds that the polypeptide with a specific sequence can initiate a tandem self-assembly process through the action of alkaline phosphatase (ALP) and Glutathione (GSH) to obtain the nano material; the simultaneous high expression of the liver cancer cells to extracellular ALP and intracellular GSH enables the polypeptide to show the strongest selectivity to the polypeptide, and can form nano-fibers in the liver cancer cells and inhibit the growth of the liver cancer cells.
In view of the above findings, it is an object of the present invention to provide a polypeptide that can construct a nanomaterial by two-step self-assembly in series by the action of ALP and GSH.
The invention also aims to provide application of the polypeptide in preparing a medicament for treating liver cancer.
Another objective of the invention is to provide a medicament for treating liver cancer, which comprises the polypeptide.
Summary of The Invention
According to a first aspect of the invention, there is provided a polypeptide having the sequence NBD-GFFpYsserGD, wherein pY represents phosphotyrosine and ss represents a disulfide bond.
The amino acid sequence of the present invention is not limited to its configuration unless otherwise specified.
The polypeptide has a structural formula (1a),
the polypeptide molecule is self-assembled in the first step, is catalyzed by ALP and then is placed at 37 ℃ for 12 hours to form a structural formula shown as (2a),
the polypeptide molecule is self-assembled in the second step, reduced by GSH, and placed at 37 ℃ for 12 hours to form the polypeptide molecule with the structural formula shown in (3a)
The polypeptide sequence self-assembled in the first step of the structural formula (2a) is NBD-GFFYsserGD, and the polypeptide sequence self-assembled in the second step of the structural formula (3a) is NBD-GFFY-Thiol.
The polypeptide NBD-GFFpYsserGD disclosed by the invention can be synthesized by a known FMOC-solid phase synthesis method, and the synthesis method can be referred to in the literature (Nanotechnology,2010,21(22): 225606.). The catalytic action of aqueous solutions of phosphorylated polypeptides by ALP and the reduction of disulfide bonds by GSH are also well known techniques.
According to a second aspect of the invention, the invention provides the use of the polypeptide NBD-GFFpYsserGD in the preparation of a medicament for treating liver cancer.
According to a third aspect of the present invention, there is provided a medicament for treating liver cancer comprising said polypeptide NBD-GFFpYsserGD.
The polypeptide can initiate a series two-step self-assembly process under the action of ALP and GSH to obtain a nano material; the simultaneous high expression of the liver cancer cells to extracellular ALP and intracellular GSH enables the polypeptide to show the strongest selectivity to the polypeptide, and can form nano-fibers in the liver cancer cells to inhibit the growth of the liver cancer cells. The amount of the polypeptide may be determined by one skilled in the art by simple experimentation, typically the polypeptide is applied as an aqueous solution at a concentration of 100-1000. mu.M (e.g.200. mu.M).
Drawings
FIG. 1: preparation of the polypeptide molecule NBD-GFFpYsserGD obtained in example 1 conversion rate in a two-step self-assembly process in series;
FIG. 2 is an electron micrograph of the polypeptide molecule NBD-GFFpYsserGD obtained in preparation example 1, which was assembled in two steps by the action of ALP and GSH. Wherein, the A picture is an electron microscope picture which is firstly added with ALP for the first step of assembly, and the B picture is an electron microscope picture which is added with GSH for the second step of self-assembly;
FIG. 3 is an electron micrograph of polypeptide molecule NBD-GFFYsserGD self-assembly by GSH (Panel A) and an electron micrograph of polypeptide molecule NBD-GFFY-thio self-assembly (Panel B);
FIG. 4: confocal laser microscopy images of hepatocytes (two normal cells, two cancer cells) cultured with the polypeptide molecule NBD-GFFpYsserGD. Wherein, the A picture is cancer cell HepG2 cultured for 0.5h, the B picture is cancer cell HepG2 cultured for 4h, the C picture is cancer cell QGY7703 cultured for 0.5h, the D picture is cancer cell QGY7703 cultured for 4h, the E picture is normal cell L02 cultured for 4h, and the F picture is normal cell QSG7701 cultured for 4 h. The bright color in the figure represents the distribution of the polypeptide molecules with yellow fluorescence in the cells, and the dark color represents the blue fluorescence after DAPI staining of the nucleus;
FIG. 5: confocal laser microscopy images of HepG2 liver cancer cells cultured for 4 hours using the polypeptide molecule NBD-GFFpYsserGD obtained in preparation example 1 and the polypeptide molecule obtained in comparative example. In which Panel A corresponds to the polypeptide molecule NBD-GFFpYsserGD of preparation example 1, Panel B corresponds to the polypeptide molecule NBD-GFFYsserGD of comparative example 1, and Panel C corresponds to the polypeptide molecule NBD-GFFY-Thiol of comparative example 2. The bright color in the figure represents the distribution of the polypeptide molecules with yellow fluorescence in the cells, and the dark color represents the blue fluorescence after DAPI staining of the nucleus;
FIG. 6: confocal microscopy images of HepG2 cells cultured for 4 hours using NBD-GFFYsserGD molecules formed after 12 hours of reaction of addition of NBD-GFFpYsserGD to ALP, which was the polypeptide molecule obtained in preparation example 1. Note: the bright color in the figure represents the distribution of the polypeptide molecules with yellow fluorescence in the cells, and the dark color represents the blue fluorescence after DAPI staining of the nucleus;
FIG. 7: the cellular uptake and the cytostatic rate of four liver cells cultured for 4 hours by polypeptide molecules are shown in a graph, wherein the A graph is the cellular uptake graph, and the B graph is the cytostatic rate graph.
Detailed Description
The invention is further described below with reference to examples, which are intended to be illustrative only and are not intended to be limiting.
In the following examples, the presence or absence of hydrogel formation was examined by inverting the vial as is commonly used in the art.
The sources of the formulations referred to in the following examples are as follows:
the equipment involved in the following examples is as follows:
high performance liquid chromatography (HPLC, Lumtech, germany);
high performance liquid chromatography mass spectrometer (LC-MS 2020, shimadzu, japan);
transmission electron microscope (Tecnai G2F20 system);
a freeze drier (LGJ-1-50, Beijing Aditakolong);
multifunctional microplate readers (BioTek, Synergy 4, USA);
confocal laser microscopy (OLYMPUS, FV1000S-IX81, Japan; Leica, Germany, TCS SP 8);
all-digital nuclear magnetic resonance spectrometer (Bruker, Bruker 400M, germany);
LC-MS (Agilent 6520Q-TOF LC/MS, Agilent, USA).
Preparation of example 1
According to the literature (Nanotechnology,2010,21(22):225606.), a polypeptide NBD-GFFpYsserGD of formula (1a) was synthesized using FMOC-solid phase synthesis:
1) the dichloro resin was first swollen in Dichloromethane (DCM) solvent for 5 minutes and added to the solid phase synthesis tube.
2) The first Fmoc-amino acid was weighed and added 2 equivalents DIEA to dissolve well in DCM and then added to the solid phase reactor for 2 hours at room temperature.
3) And (3) sealing the dichloro resin with a proper amount of methanol, and reacting for 15-30 min.
4) Washing with DCM 5 times, washing with N, N-Dimethylformamide (DMF) 5 times, and reacting with 20% piperidine for 30min to remove the Fmoc protecting group from the first amino acid.
5) After washing the remaining piperidine with DMF, a second amino acid was added while adding the same equivalent of HBTU as a coupling agent and 2 equivalents of DIEA as a catalyst, and reacted for 2 hours.
6) The steps of 4) and 5) were repeated, and after each amino acid was added, DMF in the resin was washed with DCM, and 10mL of 95% TFA was added to react for 30 minutes to cleave the peptide chain from the resin. And performing vacuum rotary evaporation to remove TFA to obtain viscous liquid, and adding anhydrous ether to separate out a precipitate to obtain the product.
The product can be used after being purified by high performance liquid chromatography.
The results of nuclear magnetic spectrum and mass spectrum of the synthesized polypeptide NBD-GFFpYsserGD are as follows:
1H NMR(400MHz,DMSO)9.45(s,1H),8.51(d,J＝8.9Hz,1H),8.25–8.03(m,7H),7.17(m,J＝24.2Hz,10H),7.05(d,J＝8.2Hz,2H),6.42(d,J＝9.3Hz,1H),4.49(m,J＝28.1,14.3,6.7Hz,4H),4.23(s,2H),3.81–3.72(m,2H),3.70(d,J＝5.5Hz,2H),3.66(s,2H),3.58(d,J＝6.7Hz,2H),3.44(d,J＝6.9Hz,16H),3.07(d,J＝5.8Hz,2H),3.02(s,1H),2.99(s,1H),2.94(s,1H),2.89(s,1H),2.82(d,J＝9.6Hz,2H),2.77–2.71(m,2H),2.71–2.63(m,2H),2.60(d,J＝6.3Hz,3H),2.36(s,3H),2.28–2.23(m,1H),1.91(d,J＝6.8Hz,1H),1.74(s,2H),1.51(s,2H),1.24(s,1H),1.06(t,J＝7.0Hz,1H).HR-MS:calcd.M+＝1538.5132,obsvd.M+＝1538.4787.
placing 0.3mg of the synthesized polypeptide NBD-GFFpYsserGD in a 1.5 ml glass bottle, adding 900 microliters of 1 XPBS (pH 7.4) solution, adjusting the pH value to 7.4 by using a sodium carbonate solution, performing ultrasonic treatment to completely dissolve the polypeptide, adding the PBS solution to supplement the PBS solution to 1 ml (the concentration is 200 micromole/liter), placing the solution in a 37 ℃ thermostat, adding 10 microliters of 0.1U/microliter alkaline phosphatase for about 12 hours after the solution temperature is stable, completing the first step of self-assembly to obtain the compound NBD-GFFYsserGD shown as the structural formula (2a), wherein the solution is a clear solution without change in properties, and the condition of polypeptide molecule conversion can be tracked and detected by a high performance liquid chromatography-mass spectrometer (LCMS); after 12 hours, glutathione of 4 times the amount of the polypeptide molecule is added into the solution, the solution is uniformly mixed and then is placed in a 37 ℃ incubator, and after 12 hours, the second step of self-assembly is completed to obtain the compound NBD-GFFY-Thiol shown as the structural formula (3a), and clear glue is formed at the moment (the method can be verified by a method of inverting a small bottle which is well known in the art). Likewise, progress of the second step self-assembly can be tracked by LCMS. The experimental procedure for conversion was as follows:
preparing 2 ml of NBD-GFFpYsserGD solution with the concentration of 200 micromole/liter, placing the solution in a constant temperature box at 37 ℃, adding 20 microliter of 0.1U microliter of alkaline phosphatase into the constant temperature box, sampling every 10 minutes, taking 100 microliter each time, simultaneously adding 100 microliter of methanol to stop the reaction of the enzyme, testing by LCMS, displaying two different peaks on the LCMS due to different molecular weights of the NBD-GFFpYsserGD and the NBD-GFFYsserGD product, determining the NBD-GFFYsserGD product according to the peak positions, and obtaining the conversion rate through the integrated area. Conversion ═ product peak area/(product peak area + reactant peak area). Similarly, the confirmation of the products and conversion of NBD-GFFYsserGD plus GSH to NBD-GFFYs-Thiol was also obtained using the above method. The conversion results of the two-step self-assembly process described above are shown in figure 1.
The microscopic morphology of the product obtained by two-step self-assembly of the polypeptide molecule NBD-GFFpYsserGD is respectively observed by a transmission electron microscope, as shown in FIG. 2. The results show that NBD-GFFpYsserGD forms nanoparticles after the first self-assembly step (FIG. 2A) and nanofibers after the second self-assembly step (FIG. 2B), and clearly demonstrate that example 1 undergoes two-step self-assembly by the action of ALP and GSH.
Comparative example 1
According to the literature (Nanotechnology,2010,21(22):225606.), the polypeptide NBD-GFFYsserGD with the structural formula shown in (2a) was synthesized by FMOC-solid phase synthesis, whose results of nuclear magnetic spectrum and mass spectrum were as follows:
1H NMR(400MHz,DMSO)8.53–7.97(m,10H),7.51(s,1H),7.28(s,1H),7.17(m,J＝14.5,5.5Hz,9H),7.04–6.97(m,3H),6.64(d,J＝8.5Hz,2H),6.41(d,J＝9.2Hz,1H),4.57–4.44(m,3H),4.38(d,J＝6.1Hz,1H),4.24(s,2H),3.82–3.63(m,5H),3.61–3.54(m,2H),3.09(d,J＝5.5Hz,3H),3.00–2.80(m,6H),2.72(ddd,J＝26.0,17.1,8.4Hz,9H),2.63–2.56(m,3H),2.39–2.20(m,7H),1.89(s,1H),1.72(s,2H),1.50(s,3H).HR-MS:calcd.M+＝1468.5333,obsvd.M+＝1458.5144.
adding a 1 XPBS (pH 7.4) solution into the polypeptide NBD-GFFYsserGD, adjusting the pH value to 7.4 by using a sodium carbonate solution, adding the PBS solution to a final concentration of 200 micromole/liter after ultrasonic treatment to completely dissolve the polypeptide NBD-GFFYsserGD, placing the mixture in a 37 ℃ thermostat, adding glutathione which is 4 times of the polypeptide molecules after the solution temperature is stable, and obtaining an assembly solution after 12 hours (the polypeptide molecules are shown as 3 a).
The microscopic morphology of the product obtained by the self-assembly of the polypeptide molecule NBD-GFFYsserGD under the GSH action is observed by a transmission electron microscope, and is shown as a graph A in figure 3. The result shows that polypeptide molecule NBD-GFFYsserGD can form nano fiber through self-assembly after GSH action.
Comparative example 2
According to the literature (Nanotechnology,2010,21(22):225606.), the polypeptide NBD-GFFY-Thiol, of formula (3a), was synthesized by FMOC-solid phase synthesis, with the following NMR and mass spectrometry results:
1H NMR(400MHz,DMSO)8.32–8.17(m,4H),8.04(d,J＝8.3Hz,1H),7.75(s,1H),7.25–7.16(m,13H),7.08(d,J＝7.7Hz,2H),4.50(m,J＝25.8,21.5,13.3,8.4Hz,5H),3.71(m,J＝16.8,5.6Hz,2H),3.63–3.56(m,4H),3.03(dd,J＝9.2,4.7Hz,3H),2.97–2.89(m,3H),2.78(dd,J＝13.9,9.9Hz,2H),2.65(dd,J＝13.7,9.6Hz,2H),1.23(s,1H).HR-MS:calcd.M+＝825.8893,obsvd.M+＝826.2869.
adding a 1 XPBS (pH 7.4) solution into the polypeptide NBD-GFFY-Thiol, adjusting the pH value to 7.4 by using a sodium carbonate solution, adding the PBS solution to a final concentration of 200 micromole/liter after completely dissolving the polypeptide by ultrasonic treatment, and placing the polypeptide NBD-GFFY-Thiol in a 37 ℃ incubator (the polypeptide molecule is shown as 3 a).
The microscopic morphology of the product obtained by the self-assembly of the polypeptide molecule NBD-GFFY-Thiol is observed by a transmission electron microscope, and is shown as a B picture in figure 3. The results show that the polypeptide molecule NBD-GFFY-thio can also form nano-fibers after self-assembly.
Application examples
Culturing cells in a special glass dish by using a culture solution prepared from 89% by volume of a culture medium (DMEM), 10% of Fetal Bovine Serum (FBS) and 1% of streptomycin mixed solution (double antibody), and placing the glass dish in a constant-temperature incubator (5% CO) at 37 DEG C2) After the cells have grown, the polypeptide molecules NBD-GFFpYsserGD, NBD-GFFYsserGD and NBD-GFFY-Thiol synthesized in preparation example 1, comparative example 1 and comparative example 2 were added to the culture medium prepared from the mixture of 89% by volume of the medium (DMEM), 10% of Fetal Bovine Serum (FBS) and 1% of streptomycin (double antibody), respectively, and cultured, with the polypeptide concentration of 200. mu.M/L, the sample was aspirated after a predetermined time of culturing, washed 3 times with 1 × PBS solution, and fixed by adding 1 ml of 4% paraformaldehyde for 20 minutes, and polymetaphylurea was aspiratedAfter washing 3 times with 1 × PBS solution, nuclear staining with DAPI solution for about 10 minutes, washing 3 times with 1 × PBS after aspirating DAPI, and finally blocking with blocking solution to prepare a confocal laser microscope, the excitation wavelength of NBD is 488 nm and the excitation wavelength of DAPI is 405nm, as shown in fig. 4, example 1 forms nanoparticles buckled on the cell membrane after culturing for 0.5 hour in two liver cancer cells (HepG2, QGY7703), as the culturing time increases, nanofibers form within the cell after 4 hours, which is identical to the previous example 1's electron micrograph, i.e., example 1 forms tandem self-assembly in liver cancer cells HepG2 and QGY7703, while normal liver cells (L02, QGY 7701) do not express ALP and GSH, so that example 1 cannot form tandem self-assembly therein, thus, no nanofibers form, as shown in fig. 5, as well as comparative example 5, as comparative example 1, as shown in fig. 5, as comparative example 2, as the fluorescence molecules formed in situ, as shown in fig. the present invention, the fluorescent nanoparticles are formed from fluorescent nanoparticles.
Cell uptake assay
The cells were cultured in a 37 ℃ incubator (5% CO) using a culture medium prepared from 89% by volume of a culture medium (DMEM), 10% Fetal Bovine Serum (FBS) and 1% streptomycin (double antibody)2) After the cells have grown, the polypeptide molecules NBD-GFFpYssERGD, NBD-GFFYssERGD and NBD-GFFY-Thiol synthesized in preparation example 1, comparative example 1 and comparative example 2 were added to a culture solution prepared by mixing 89% by volume of a culture medium (DMEM) + 10% Fetal Bovine Serum (FBS) + 1% streptomycin qing (double antibody) for 4 hours, respectively, and the polypeptide concentration was 200. mu. mol/l.4 hours, the sample was aspirated, washed 3 times with 1 × PBS solution, 1 ml of cell lysate and 200. mu.l of DMSO were added to each well and mixed and then taken out into a centrifuge tube, 1500g (a unit of centrifuge RCF, expressed by a multiple of g of gravitational acceleration g) was centrifuged for 15 minutes, the supernatant was taken, and the supernatant was tested with a microplate reader.A.A.A.A.A.preparation example 1 shows a higher uptake of liver cancer cells, while a lower uptake of liver cancer cells in normal cells, and a similar uptake of the polypeptide molecules in the cells of the present invention shows a stronger inhibition of liver cancer cells than the normal liver cancer cells, and a similar to the polypeptide molecules of the present invention.
Cell viability assay
The cells were cultured in a 37 ℃ incubator (5% CO) using a culture medium prepared from 89% by volume of a culture medium (DMEM), 10% Fetal Bovine Serum (FBS) and 1% streptomycin (double antibody)2) After the cells had grown, the polypeptide molecules NBD-GFFpYsserGD, NBD-GFFYsserGD and NBD-GFFY-Thiol synthesized in preparation example 1, comparative example 1 and comparative example 2 were added to a culture solution prepared from a mixture of 89% by volume of a culture medium (DMEM), 10% of Fetal Bovine Serum (FBS) and 1% of streptomycin (double antibody), respectively, and the mixture was cultured in such a manner that the concentration of the polypeptide was 200. mu.M, the sample was aspirated after 48 hours of culture, washed 3 times with 1 × PBS solution, and then CCK8 solution was added, and after 4 hours, the cells were labeled with enzymeThe absorption at 405nm is measured, the ratio of the average value of experimental group data to the average value of blank group data is the cell survival rate, and the 1-cell survival rate is the cell inhibition rate. As shown in panel B of FIG. 7, the inhibition rates of the two hepatoma cells HepG2 and QGY7703 were 79.68% and 62.08% for the polypeptide molecule NBD-GFFpYsserGD described in preparation example 1, 55.51% and 36.12% for the polypeptide molecule NBD-GFFYsserGD described in comparative example 1, and 32.28% and 29.66% for the polypeptide molecule NBD-GFFY-Thiol described in comparative example 2; it is shown that the inhibition ability of the preparation example 1 to the liver cancer cells is stronger than that of the comparative examples 1 and 2; in addition, the inhibition rates of preparation example 1 on two normal liver cells are 11.77% and 9.08%, respectively, and the inhibition rates of comparative example 1 and comparative example 2 on normal cells are higher than that of example 1, which shows that the polypeptide molecule NBD-GFFpYsseRNGD of the present invention can selectively inhibit the growth of liver cancer cells, and has lower inhibition capability on normal cells.
There have been many reports that the transformation of nanoparticles or nanofibers in tumor tissues or cancer cells can promote better retention of nanoprobes and nanopharmaceuticals within tumors. Although nanoparticles exhibit enhanced permeability and retention effects on tumors, they have limited tumor penetration capabilities. Since free molecules can diffuse freely in tissues, molecules with tandem self-assembly processes may exhibit greater advantages in cancer diagnosis and therapy. The present invention describes a polypeptide molecule that induces tandem self-assembly by enzymatic and chemical reactions, namely example 1 (NBD-GFFpYsserGD). Example 1 self-assembled nanoparticles first by ALP in PBS buffer solution and then into nanofibers by GSH. It is well known that hepatoma cells exhibit higher concentrations of extracellular ALP and intracellular GSH compared to normal cells. Thus, preparative example 1, in which nanoparticles are first formed around liver cancer cells and then nanofibers are formed within the liver cancer cells, also occurred in tandem self-assembly in the liver cancer cell lines HepG2 and QGY 7703. Preparation example 1 having such tandem self-assembly property shows higher cellular uptake and cytostatic capacity to cancer cells between liver cancer cells and liver normal cells. This is not the case in comparative examples 1 and 2. Even though the transmission electron microscope results of comparative example 1 and comparative example 2 show that they can form nanofibers, they do not form nanofibers in the liver cancer cell because they cannot achieve two-step self-assembly by using the difference of microenvironment inside and outside the liver cancer cell, and thus the cell inhibition ability is much reduced compared to that of preparation example 1. Therefore, the molecules with the series self-assembly property have stronger selectivity on liver cancer cells, so that the molecules have stronger performance in diagnosis and treatment of liver cancer.
Claims (3)
1. A polypeptide having the sequence NBD-GFFpYsserGD, wherein pY represents phosphotyrosine, ss represents a disulfide bond,
the polypeptide has a structural formula (1a),
2. a medicament for treating liver cancer comprising the polypeptide of claim 1.
3. The use of the polypeptide of claim 1 in the preparation of a medicament for the treatment of liver cancer.
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