Polypeptide for blocking IgE-FcER1 binding and application thereof

Abstract

The invention relates to the field of biological medicines, in particular to a polypeptide for blocking IgE-FcER1 binding and application of the polypeptide. The amino acid sequence of the polypeptide has a first amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 2 or a second amino acid sequence consisting of 20-40 continuous amino acids in the first amino acid sequence. The polypeptide provided by the invention can effectively block the binding of IgE-FcER1 and eliminate the effect of excessive immunity, thereby preventing and / or treating diseases related to a signal path of the polypeptide.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to a polypeptide for blocking IgE-FcER1 binding and an application thereof. Background Art

[0002] Immunoglobulin E (IgE) is a type of immunoglobulin (Ig) discovered in 1966. It has a molecular weight of 190kD and is present in very low levels in serum, accounting for only 0.004% of the total serum Ig. It is synthesized relatively late in individual development. The basic structure of an Ig molecule is composed of four peptide chains, namely, two identical peptide chains with smaller molecular weights (called light chains) and two identical peptide chains with larger molecular weights (called heavy chains). The light chain and the heavy chain are connected by disulfide bonds to form a monomer of a four-peptide chain molecule called an Ig molecule, which is the basic structure of an immunoglobulin molecule. The directions of the free amino or carboxyl groups at both ends of the four peptide chains in the Ig monomer are consistent, and are named the amino terminus (N terminus) and the carboxyl terminus (C terminus) respectively. The ε chain has 4 CHs (Cε1-Cε4), no hinge region, and contains more cysteine ​​and methionine. It is sensitive to heat, and IgE can lose its biological activity at 56°C for 30 minutes.

[0003] IgE is mainly produced by plasma cells in the lamina propria of mucosa such as nasopharynx, tonsils, bronchi, gastrointestinal tract, etc. These sites are often the sites of allergen invasion and type I allergic reactions. IgE is a cell-tropic antibody that can bind to the high-affinity FcER1 on the surface of basophils or mast cells through the Cε2 and Cε3 functional regions, and more specifically to the α chain (FcER1α) of FcER1 with high affinity, making the aforementioned cells in a sensitized state. Basophils or mast cells in a sensitized state are activated by IgE bridging with the corresponding strain, degranulating and releasing bioactive mediators, which can act on effector organs such as skin, blood vessels, respiratory tract, and digestive tract, causing a series of pathological changes such as smooth muscle spasm, capillary dilation, increased vascular permeability, and increased glandular secretion, ultimately causing type I allergic reactions (such as anaphylactic shock, skin allergic reactions, respiratory allergic reactions, and digestive tract allergic reactions), and even threatening life. Therefore, the research and development of IgE-FcER1 inhibitors is of great significance for the prevention, treatment and improvement of the above diseases.

[0004] Polypeptides are biologically active substances that constitute various cellular functions in the body. They have the characteristics of small relative molecular mass, high specificity, easy absorption, easy synthesis and modification, ability to enhance the body's immunity, and high safety. They have high application value in clinical treatment.

[0005] In view of this, it is of great significance to develop a drug peptide targeting the IgE-FcER1 binding signaling pathway. Summary of the invention

[0006] The object of the present invention is to provide a drug polypeptide capable of blocking IgE-FcER1 binding, and this drug polypeptide has a high affinity for IgE and / or FcER1.

[0007] To achieve the above object, a first aspect of the present invention provides a polypeptide for blocking IgE-FcER1 binding or a pharmaceutically acceptable salt thereof, and the amino acid sequence of this polypeptide has at least one of the following amino acid sequences:

[0008] (1a) The first amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2;

[0009] (1b) An amino acid sequence having at least 90% sequence identity with the first amino acid sequence;

[0010] (1c) A tag protein or a modified amino acid sequence is linked to the amino terminus and / or carboxyl terminus of the amino acid sequences shown in (1a) and (1b);

[0011] (1d) An amino acid sequence having the same function obtained by processing the amino acid sequences shown in (1a), (1b) and (1c); the processing is at least one of substituting at least one amino acid, deleting at least one amino acid and adding at least one amino acid.

[0012] A second aspect of the present invention provides a gene, and the nucleotide sequence of this gene is a nucleotide sequence capable of encoding the amino acid sequence of the polypeptide for blocking IgE-FcER1 binding described in the first aspect above.

[0013] A third aspect of the present invention provides a vector, and this vector contains the gene described in the second aspect above.

[0014] A fourth aspect of the present invention provides a host cell, and this host cell contains the vector described in the third aspect above.

[0015] A fifth aspect of the present invention provides a pharmaceutical composition, and this pharmaceutical composition contains a therapeutically effective amount of the polypeptide for blocking IgE-FcER1 binding described in the first aspect above or a pharmaceutically acceptable salt thereof. A sixth aspect of the present invention provides the use of at least one of the polypeptide for blocking IgE-FcER1 binding described in the first aspect above or a pharmaceutically acceptable salt thereof, the gene described in the second aspect above, the vector described in the third aspect above, the host cell described in the fourth aspect above, and the pharmaceutical composition described in the fifth aspect above in the preparation of a drug for preventing and / or treating a disease related to the signal pathway associated with IgE-FcER1 binding.

[0016] The polypeptide provided by the present invention is obtained by screening, which can effectively block the binding of IgE-FcER1, eliminate the effect of over-immunity, and thus can prevent and / or treat diseases related to its signaling pathway.

[0017] Other features and advantages of the present invention will be described in detail in the following specific implementation section. Brief Description of the Drawings

[0018] Figure 1 It is an ELISA result diagram of the polypeptide containing the amino acid sequences shown in SEQ ID NO: 1 and SEQ ID NO: 2 provided by the present invention and IgE-FcER1α;

[0019] Figure 2 It is an ELISA result diagram of the polypeptide containing the amino acid sequences shown in SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 9 and SEQ ID NO: 10 provided by the present invention and IgE-FcER1α;

[0020] Figure 3 It is an ELISA result diagram of the polypeptide containing the amino acid sequences shown in SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 11 and SEQ ID NO: 12 provided by the present invention and IgE-FcER1α;

[0021] Figure 4 It is an ELISA result diagram of the polypeptide containing the amino acid sequences shown in SEQ ID NO: 8 and SEQ ID NO: 13 provided by the present invention and IgE-FcER1α. Specific Embodiments

[0022] In the ranges disclosed herein, the endpoints and any values are not limited to the exact 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 each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed herein.

[0023] It should be noted that unless otherwise defined herein, the scientific and technical terms used in the present invention should have the meanings commonly understood by those skilled in the art.

[0024] In the present invention, the "sequence identity" refers to the degree to which two sequences (such as amino acids) have the same residues at the same positions after alignment. For example, "an amino acid sequence is X% identical to SEQ ID NO: Y" means that the amino acid sequence has X% identity with SEQ ID NO: Y, and is described as X% of the residues in the amino acid sequence being the same as the residues of the sequence disclosed in SEQ ID NO: Y. Generally, such calculations are performed using computer programs. Exemplary computer programs for comparing and aligning sequence pairs can be ALIGN (Myers and Miller, 1988), FASTA (Pearson and Lipman, 1988; Pearson, 1990), and gapped BLAST (Altschul et al., 1997), BLASTP, BLASTN, or GCG (Devereux et al., 1984). In addition, when determining the degree of sequence identity between two amino acid sequences, those skilled in the art can consider "conservative" amino acid substitutions, which can generally be described as amino acid substitutions in which an amino acid residue is replaced by another amino acid residue having a similar chemical structure, which has little or no effect on the function, activity, or other biological properties of the polypeptide. Such "conservative" amino acids can be amino acids known in the art.

[0025] As described above, the first aspect of the present invention provides a polypeptide that blocks IgE-FcεR1 binding or a pharmaceutically acceptable salt thereof, and the amino acid sequence of the polypeptide has at least one of the following amino acid sequences:

[0026] (1a) The first amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2;

[0027] (1b) An amino acid sequence having at least 90% sequence identity with the first amino acid sequence;

[0028] (1c) A tag protein or a modified amino acid sequence is linked to the amino terminus and / or carboxyl terminus of the amino acid sequences shown in (1a) and (1b);

[0029] (1d) An amino acid sequence having the same function obtained after processing the amino acid sequences shown in (1a), (1b), and (1c); the processing is at least one of substituting at least one amino acid, deleting at least one amino acid, and adding at least one amino acid.

[0030] Preferably, the amino acid sequence of the polypeptide is an amino acid sequence having at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity with the first amino acid sequence.

[0031] The first amino acid sequence shown as SEQ ID NO: 1 or SEQ ID NO: 2 in the present invention is a polypeptide detected by high-throughput screening technology from a polypeptide library and having the effect of blocking IgE-FcER1 binding. The discovery steps of this polypeptide include: dissolving and diluting the polypeptide library to obtain a mixed solution; then sequentially mixing the mixed solution with reactant I containing IgE, reactant II containing FcER1 and its label, and reactant III capable of undergoing a color reaction with the label to obtain a detection solution; finally, using an enzyme-linked immunosorbent assay (ELISA) instrument to detect the absorbance of the detection solution at a specific wavelength, and obtaining the target polypeptide according to the inhibition rate calculated from the absorbance.

[0032] It should be noted that the present invention has no particular limitation on the method of dissolution and dilution. Those skilled in the art can select according to the known technical means in the art. An exemplary preferred specific implementation manner is provided in the following text of the present invention, and those skilled in the art should not understand it as a limitation of the present invention.

[0033] In the present invention, the polypeptide library is a polypeptide library containing nearly 73,000 80-amino acid polypeptides constructed by Hunan Zhongcheng Peptide Biochemical Co., Ltd. using PICT (Peptide Information Compression Technology). The specific construction method can be specifically referred to in CN107849737A and CN111727194A.

[0034] It should be noted that the present invention has no particular limitation on the synthesis method of the polypeptide. Those skilled in the art can select according to the known technical means in the art. Exemplarily, the polypeptide in the present invention is synthesized by the method disclosed in CN117069806A.

[0035] It should be noted that the present invention has no particular limitation on the type of tag protein. Those skilled in the art can select according to the known technical means in the art. The tag protein does not affect the activity of the polypeptide provided by the present invention. In actual application, those skilled in the art can choose whether to connect a tag protein at the amino terminus and / or carboxyl terminus of the amino acid sequence according to the need.

[0036] Preferably, the amino acid sequence of the polypeptide further has at least one of the following amino acid sequences:

[0037] (2a) A second amino acid sequence consisting of 20-40 consecutive amino acids in the first amino acid sequence;

[0038] (2b) An amino acid sequence having at least 90% sequence identity with the second amino acid sequence;

[0039] (2c) A tag protein or a modified amino acid sequence is linked to the amino terminus and / or carboxyl terminus of the amino acid sequences shown in (2a) and (2b);

[0040] (2d) An amino acid sequence having the same function obtained after processing the amino acid sequences shown in (2a), (2b), and (2c); the processing is at least one of substituting at least one amino acid, deleting at least one amino acid, and adding at least one amino acid.

[0041] More preferably, the amino acid sequence of the polypeptide is an amino acid sequence having at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity with the second amino acid sequence.

[0042] Further preferably, the second amino acid sequence is as shown in SEQ ID NO: 3 - SEQ ID NO: 13.

[0043] According to a particularly preferred embodiment, the polypeptide having the first amino acid sequence is a cyclic peptide.

[0044] According to another particularly preferred embodiment, the polypeptide having the second amino acid sequence is a linear peptide.

[0045] Preferably, the pharmaceutically acceptable salt is selected from at least one of trifluoroacetate, acetate, hydrochloride, and phosphate.

[0046] In the present invention, the amino acid sequences shown in SEQ ID NO: 1 - SEQ ID NO: 13 are shown in Table 1 below:

[0047] Table 1

[0048]

[0049] Preferably, the modification is selected from at least one of amination modification, hydroxylation modification, carboxylation modification, carbonylation modification, amidation modification, alkylation modification, phosphorylation modification, glycosylation modification, cyclization modification, biotinylation modification, acetylation modification, esterification modification, fluorescent group modification, polyethylene glycol modification, and immobilization modification.

[0050] As described above, the second aspect of the present invention provides a gene, and the nucleotide sequence of the gene is a nucleotide sequence capable of encoding the amino acid sequence of the polypeptide that blocks the binding of IgE-FcER1 described in the first aspect above.

[0051] As described above, the third aspect of the present invention provides a vector, and the vector contains the gene described in the second aspect above.

[0052] As described above, the fourth aspect of the present invention provides a host cell, and the host cell contains the vector described in the third aspect above.

[0053] As described above, the fifth aspect of the present invention provides a pharmaceutical composition, and the pharmaceutical composition contains a therapeutically effective amount of the polypeptide that blocks the binding of IgE-FcER1 described in the first aspect above or a pharmaceutically acceptable salt thereof.

[0054] Preferably, the composition further contains an excipient.

[0055] It should be noted that the present invention has no particular limitation on the type of the excipient, and those skilled in the art can select according to the known technical means in the art, as long as the polypeptide provided in the present invention can target IgE and / or FcER1.

[0056] As described above, the sixth aspect of the present invention provides the use of at least one of the polypeptide that blocks the binding of IgE-FcER1 described in the first aspect above or a pharmaceutically acceptable salt thereof, the gene described in the second aspect above, the vector described in the third aspect above, the host cell described in the fourth aspect above, and the pharmaceutical composition described in the fifth aspect above in the preparation of a drug for preventing and / or treating a disease related to the signal pathway associated with the binding of IgE-FcER1.

[0057] Preferably, the disease related to the signal pathway associated with the binding of IgE-FcER1 is selected from at least one of anaphylactic shock, skin allergic reaction, respiratory allergic reaction, digestive tract allergic reaction, pathological cardiac remodeling and dysfunction.

[0058] More preferably, the disease related to the signal pathway associated with the binding of IgE-FcER1 is selected from at least one of urticaria, pulmonary hypertension, heart failure, and myocardial hypertrophy.

[0059] The present invention will be described in detail below by way of examples.

[0060] In the following examples, unless otherwise specified, the raw materials used are all commercially available.

[0061] In the following examples, unless otherwise specified, the room temperature is expressed as 25 ± 5 °C.

[0062] Experimental reagents:

[0063] Reagent I: Recombinant Human IgE, Fc protein (His Tag), manufacturer: Sino Biological Inc., catalog number: 29702-H08H1;

[0064] Reagent II: Human Fc epsilon R1 alpha Protein, Fc tag (MALS&BLI verified), manufacturer: Absin Biosciences Inc., catalog number: FCA-H5259;

[0065] Reagent III: Perodoxidase-conjugated AffiniPure Goat anti-Human IgG, FcγFragment, manufacturer: Jackson ImmunoResearch Inc., catalog number: 109-035-008.

[0066] Example 1: ELISA screening of polypeptides

[0067] Dissolution of the polypeptide library: Place the polypeptides in the polypeptide library in a 96-well deep well plate, centrifuge at 4000 rpm for 3 min, and then add 200 μL / well of ultrapure water (polypeptide concentration is 50 μM); then seal with a silica gel lid, incubate in a 95 °C water bath for 5 min, and then centrifuge at 4000 rpm for 3 min;

[0068] Dilution of the polypeptide library: Transfer the centrifuged polypeptides to a 384-well plate using a workstation, and dilute the polypeptide concentration to the experimental concentration with loading buffer (loading buffer: Tris-HCl buffer, pH = 7.4) to obtain each mixture;

[0069] Screening of polypeptides: Reagent I (at a concentration of 0.2 μg / mL) was immobilized on a 384-well plate at 25 μL / well; then each of the above-mentioned mixed solutions was transferred to the 384-well plate immobilized with Reagent I at 12.5 μL / well using a workstation, and then a premixed solution (Reagent II (at a concentration of 0.032 μg / mL) and Reagent III diluted 5000-fold were mixed at a volume ratio of 1:1 at room temperature for 1 h) was added to the above-mentioned 384-well plate at 12.5 μL / well. After instantaneous centrifugation to remove air bubbles, it was placed in an incubator at 37 °C for 2 h. After discarding the liquid in the wells, 80 μL of 1×TBST washing solution with pH = 7.4 was added to wash the plate 4 times, 4 min each time. The 384-well plate was dried, 25 μL of chromogenic solution (manufacturer: Solarbio, catalog number: PR1210) was added to each well, and it was continued to be placed in the incubator at 37 °C for 30 min. Finally, 25 μL of termination solution (1 M HCl) was added to each well to terminate the reaction. The absorbance of each well at 450 nm was read using a microplate reader (model: cytation5). After calculating the inhibition rate of each polypeptide concentration according to the formula, the IC50 values of each polypeptide were calculated by plotting using graphpad prism software, and 2 target polypeptides were screened, that is, polypeptides (cyclic peptides) with amino acid sequences as shown in SEQ ID NO: 1 and SEQ ID NO: 2; among them, the inhibition rate calculation formula is: Inhibition% = (1 - (compound signal - background signal) / (positive signal - background signal)) * 100.

[0070] Example 2: Uncompression of polypeptides and further ELISA screening

[0071] Polypeptides with amino acid sequences containing 5 - 80 amino acids were designed and synthesized according to the 2 target polypeptides obtained in Example 1; and 11 target polypeptides (screening criteria are the same as in Example 1) were further screened according to the polypeptide screening method in Example 1, that is, polypeptides (linear peptides) with amino acid sequences as shown in SEQ ID NO: 3 - SEQ ID NO: 13.

[0072] Table 1: IC50 values of sequences

[0073] IC50 (μM) SEQ ID NO: 1 0.66 SEQ ID NO: 2 1.49 SEQ ID NO: 3 13.82 SEQ ID NO: 4 1.63 SEQ ID NO: 5 5.39 SEQ ID NO: 7 7.90 SEQ ID NO: 9 14.72 SEQ ID NO: 10 15.80 SEQ ID NO: 12 9.90 SEQ ID NO: 13 14.07

[0074] Figures 1 to 4 It is a graph of the ELISA results of the polypeptides with amino acid sequences as shown in SEQ ID NO: 1 - SEQ ID NO: 13 provided by the present invention and IgE-FcER1α. Among them, Antagonist in the graph represents the concentration of the polypeptide, and Inhibition represents the inhibition rate. The IC50 values of each polypeptide can be calculated from the graph, and the specific results are shown in Table 1.

[0075] As can be seen from the results in Table 1, the polypeptide provided by the present invention can effectively block the binding of IgE-FcεRI.

[0076] Example 3 Polypeptide Synthesis

[0077] The polypeptide compounds and their derivatives provided by the present invention are synthesized by solid-phase synthesis to obtain their linear precursors, and the target crude peptide is obtained after cleavage. The synthesis carrier is 2-Chlotrityl Resin. During the synthesis process, first, the 2-Chlotrityl Resin is fully swollen in N,N-dimethylformamide (DMF), and then the solid-phase carrier is repeatedly subjected to the operations of condensation → washing → deprotection of Fmoc → washing → condensation of the next amino acid to reach the desired polypeptide chain length. Finally, a mixed solution of trifluoroacetic acid: water: triisopropylsilane: benzyl methyl sulfide (90:2.5:2.5:5, v:v:v:v) is reacted with the resin to cleave the polypeptide from the solid-phase carrier, and the target polypeptide crude product is obtained after precipitation with cold methyl tert-butyl ether. The polypeptide crude product is purified and separated by a C18 reversed-phase preparative chromatography column in a system of acetonitrile / water with 0.1% trifluoroacetic acid to obtain the pure product of the polypeptide and its derivatives.

[0078] Experimental Reagents

[0079]

[0080]

[0081] (1) Synthesis of the polypeptide shown in SEQ ID No. 4

[0082]

[0083] Step 1: Coupling of the first amino acid Fmoc-His(Boc)-OH

[0084] 84 mg (0.1 mmol) of 2-Chlorotrityl chloride resin was fully swollen in DCM for 1 h. Weigh Fmoc-His-OH (0.08 mmol) and diisopropylethylamine (DIEA, 0.32 mmol), dissolve them in 5 ml of DCM and add to the resin, and react at room temperature for 2 h. After the reaction is completed, add the blocking solution (10 ml) DCM: methanol: DIEA (85:10:5, v:v:v) and block at room temperature for 10 min. The blocked resin is washed 5 times with DCM and 5 times with DMF.

[0085] Step 2: Synthesis of the linear precursor peptide chain

[0086] Linear precursor peptide chain of SEQ ID No. 4

[0087] H-H-Y-Y-N-D-E-T-E-M-D-R-N-E-V-N-G-M-E-I-N-I-M-H-V-E-M-W-A-C。

[0088] The resin obtained in Step 1 was fully swollen in DMF for 1 h, and then synthesized in the order from the second W at the carboxyl terminus to the amino terminus according to the linear precursor sequence. Each coupling cycle was carried out as follows:

[0089] ·Fmoc-deprotection was performed twice with 20% piperidine / DMF (20% v / v, 10 mL), 8 min each time.

[0090] ·The resin was rinsed with DMF 6 - 8 times until neutral pH.

[0091] ·Dissolve 0.5 mmol of Fmoc-AA, 0.5 mmol of 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU) and 1 mmol of 4-methylmorpholine (NMM) in DMF, add to the resin and react at room temperature for 1 h.

[0092] ·The resin was rinsed with DMF 4 - 6 times before the next amino acid coupling.

[0093] After the linear polypeptide was synthesized, the resin was rinsed with DMF 5 times and with DCM 5 times. The resin was dried in vacuo.

[0094] Step 3: Cleavage of the linear precursor peptide chain

[0095] Freshly prepared cleavage cocktail (10 mL) trifluoroacetic acid: water: triisopropylsilane: benzyl methyl sulfide (90:2.5:2.5:5, v:v:v:v) was added to the resin obtained in Step 2, and the reaction was shaken at room temperature for 2 h. After the reaction was completed, the reaction solution was filtered, and the resin was washed with trifluoroacetic acid and combined with the reaction solution. The crude product was precipitated with 4 volumes of cold MTBE. The crude product was washed 3 times with MTBE and dried in vacuo.

[0096] Step 4: Purification and preparation of the polypeptide

[0097] The polypeptide crude product was dissolved in 20% aqueous acetonitrile solution, filtered through a 0.45 μm membrane and separated by a reverse-phase high-performance liquid chromatography system. The buffers were A (0.1% trifluoroacetic acid, aqueous solution) and B (0.1% trifluoroacetic acid, acetonitrile). Among them, the chromatographic column was a BR-C18 (Sepax) reverse-phase chromatographic column. During the purification process, the detection wavelength of the chromatograph was set at 230 nm, the flow rate was 15 mL / min, and the gradient was 20 - 50% acetonitrile in 40 min. The relevant fractions of the product were collected, and the fractions with >95% purity were combined after HPLC identification, freeze-dried to obtain the pure polypeptide product.

[0098] Other polypeptides of the present invention can be synthesized with reference to the synthesis method of SEQ ID No. 4.

[0099] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited thereto. Within the technical concept scope of the present invention, various simple modifications can be made to the technical solutions of the present invention, including any other suitable combination of each technical feature. These simple modifications and combinations should also be regarded as the content disclosed by the present invention and fall within the protection scope of the present invention.

Claims

1. A polypeptide that blocks IgE-FcER1 binding or a pharmaceutically acceptable salt thereof, characterized in that, The amino acid sequence of the polypeptide has at least one of the following amino acid sequences: (1a) The first amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2; (1b) An amino acid sequence having at least 90% sequence identity with the first amino acid sequence; (1c) A tag protein or a modified amino acid sequence linked to the amino terminus and / or carboxyl terminus of the amino acid sequences shown in (1a) and (1b); (1d) An amino acid sequence with the same function obtained by processing the amino acid sequences shown in (1a), (1b), and (1c); the processing is at least one of substituting at least one amino acid, deleting at least one amino acid, and adding at least one amino acid.

2. The polypeptide or a pharmaceutically acceptable salt thereof according to claim 1, wherein, The amino acid sequence of the polypeptide also has at least one of the following amino acid sequences: (2a) A second amino acid sequence consisting of 20-40 consecutive amino acids in the first amino acid sequence; (2b) An amino acid sequence having at least 90% sequence identity with the second amino acid sequence; (2c) A tag protein or a modified amino acid sequence linked to the amino terminus and / or carboxyl terminus of the amino acid sequences shown in (2a) and (2b); (2d) An amino acid sequence with the same function obtained by processing the amino acid sequences shown in (2a), (2b), and (2c); the processing is at least one of substituting at least one amino acid, deleting at least one amino acid, and adding at least one amino acid.

3. The polypeptide or a pharmaceutically acceptable salt thereof according to claim 2, wherein, The second amino acid sequence is shown in SEQ ID NO: 3 - SEQ ID NO:

13.

4. The polypeptide or a pharmaceutically acceptable salt thereof according to claim 2 or 3, wherein, The polypeptide having the first amino acid sequence is a cyclic peptide; and / or, The polypeptide having the second amino acid sequence is a linear peptide.

5. A gene, characterized in that, The nucleotide sequence of the gene is a nucleotide sequence capable of encoding the amino acid sequence of the polypeptide that blocks IgE-FcER1 binding as described in any one of claims 1-4.

6. A vector, characterized in that, The vector contains the gene as described in claim 5.

7. A host cell, characterized in that, The host cell contains the vector as described in claim 6.

8. A pharmaceutical composition, characterized in that, The pharmaceutical composition contains a therapeutically effective amount of the polypeptide that blocks IgE-FcER1 binding as described in any one of claims 1-4 or a pharmaceutically acceptable salt thereof.

9. Use of at least one of the polypeptide that blocks IgE-FcER1 binding or a pharmaceutically acceptable salt thereof according to any one of claims 1-4, the gene according to claim 5, the vector according to claim 6, the host cell according to claim 7, and the pharmaceutical composition according to claim 8 in the preparation of a drug for preventing and / or treating a disease related to the signal pathway associated with IgE-FcER1 binding.

10. The use according to claim 9, wherein, The diseases related to the signal pathway associated with IgE-FcER1 binding are selected from at least one of anaphylactic shock, cutaneous allergic reaction, respiratory allergic reaction, gastrointestinal allergic reaction, pathological cardiac remodeling, and dysfunction.

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