CN115724913B - Polypeptide for inhibiting MC3 receptor activation and application thereof - Google Patents
Polypeptide for inhibiting MC3 receptor activation and application thereof Download PDFInfo
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Abstract
The invention discloses a polypeptide for inhibiting MC3 receptor activation and application thereof, wherein the amino acid sequence of the polypeptide is shown as any one of SEQ ID NO. 1-18. The invention applies high flux drug screening technology to screen the polypeptide named as 80 cyclic peptide 3 (PL 00803001) from a large cyclic peptide library, which can inhibit MC3 receptor and block activation of cell signal path. PL00803001 is a cyclic peptide containing 80 amino acids, and a series of derivative small cyclic peptides and linear peptides are obtained by decompression technology, and all have the function of MC3 receptor inhibitors. PL00803001 and its series of polypeptides can act as MC3 receptor inhibitors, and can further develop novel polypeptides useful in metabolic diseases including, but not limited to, obesity.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to a polypeptide for inhibiting MC3 receptor activation and application thereof.
Background
Protein-coupled receptors (G proteins-coupled receptors, GPCRs) are a class of 7-pass transmembrane receptors, belonging to the cell membrane surface receptor, accounting for about 4% of the proteins encoded by the human genome. There are about 475 targets for FDA approved drugs, with about 108 GPCRs accounting for 34%. The global sales of GPCRs receptor drugs exceeds 1800 hundred million dollars each year, and the GPCRs receptor drugs account for more than 27% of the global drug market, so that the development of the GPCRs receptor drugs has broad prospect.
Melanocortin receptors (Melanocortin receptor, MCR) share 5 subtypes, which were subsequently discovered and cloned in the 90 s of the last century. The clones were designated MC1R, MC2R, MC3R, MC4R and MC5R in the order named. They belong to class a GPCR (G protein coupled receptor) proteins, located on the cell surface, coupled G proteins are mainly gαs, thus transmitting their physiological signals by altering intracellular cAMP. MCR is widely distributed and functionally diverse, with each subtype having endogenous agonistic and inhibitory ligands. These ligands and 5 subtypes of MCR together constitute the melanocortin hormone system that in humans comprises: a. agonistic polypeptide ligands, i.e., α -, β -, γ -MSH (α, β, γ -melanocyte stimulating hormone) and ACTH (adrenocorticotropic hormone); b. melanocortin receptors of the 5 subtypes described above; c. endogenous inhibitory ligand proteins agouti (a spiny mouse protein, also known as ASIP in humans, agouti signal protein, a spiny mouse signal protein) and AgRP (agouti-related protein, a spiny mouse related protein). MC3R is mainly distributed in brain, placenta, stomach, pancreas, duodenum, heart, ovary, breast, kidney, muscle cell, immune cell and other tissues, and plays the functions of energy metabolism steady state balance, anti-inflammation and the like. It was found that MC3R (melanocortin receptor 3) is predominantly distributed in the hypothalamic ventral medial nucleus and thalamus arciform nucleus (ARC), which contains two classes of neurons that regulate energy metabolism and control appetite: one class is the appetite-promoting agouti-related protein (AgRP) neurons; the other is pro-opiomelanocortin (POMC) neurons that suppress appetite. More expression of MC3R was in dietary-promoting AgRP neurons, with 97% of neurons expressing MC3R. Roger et al found that MC3R knockout mice (either female or male) developed anorexia and reduced body weight. Wild-type mice developed severe anorexia after ventricular injection of the MC3R specific antagonist C11 in mice, and reduced diet by about 4-fold at 6 hours post-dose, revealing the potential of the MC3R target for use in a range of diets and treatment of obesity.
Obesity is listed as one of the ten major risk factors responsible for the disease burden and is also one of the most serious public health problems at present. Obesity, which refers to abnormal or excessive fat accumulation, is a chronic metabolic disease caused by the interaction of various factors including genetic and environmental factors. It has been reported that the global population of obese people rapidly climbs from 9.9 million to 12.1 million with a annual compound growth rate of 5.0% by 2016 to 2020, accounting for about 16% of the global population; wherein, the number of people suffering from obesity in China reaches 2.2 hundred million, and accounts for 18% of people in China. The obese population will continue to grow, with global obese people over 15 million in 2025 and approaching 20 million in 2030. The number of obese people in 2025 was 2.7 million people in China and 3.3 million people in 2030.
Currently, obesity drug development has focused on obesity treatment with GLP-1 receptor agonist drugs. Several companies are developing drugs for treating obesity against MC4R, and there are no drugs for MC3 receptor. The molecular weight of the polypeptide medicine is between that of the small molecular medicine and that of the large molecular biological medicine such as antibody protein, and the polypeptide is taken as a signal molecule to participate in a plurality of physiological functions in the organism, so the polypeptide medicine often plays a role of alternative therapy to compensate the lack of endogenous polypeptide hormone level, and in 2019, the polypeptide medicine accounts for 5% of the global medicine market and is sold in more than 500 hundred million dollars. Accordingly, the present invention provides a polypeptide that inhibits MC3 receptor activation and uses thereof.
Disclosure of Invention
The invention aims to: the invention aims to solve the technical problem of providing a polypeptide aiming at the defects of the prior art.
The invention also solves the technical problem of providing a nucleotide.
The invention also solves the technical problem of providing an MC3 receptor inhibitor.
The invention also solves the technical problem of providing a pharmaceutical composition for preventing or treating metabolic diseases.
The invention also solves the technical problem of providing the application of the polypeptide, or the MC3 receptor inhibitor, or the pharmaceutical composition in preparing medicines for preventing or treating metabolic diseases.
The invention finally aims to provide a medicament for preventing or treating metabolic diseases.
The invention is characterized in that: the polypeptide medicine is modified based on natural active polypeptide, and the present invention uses large polypeptide library with independent intellectual property rights and high flux screening technology to obtain MC3 acceptor inhibitor number PL00803001 polypeptide and linear and annular polypeptide with different amino acid numbers.
In order to solve the first technical problem, the invention discloses a polypeptide, the amino acid sequence of which is shown as any one of SEQ ID NO.1-18, preferably a polypeptide with the amino acid sequence shown as any one of SEQ ID NO.1, SEQ ID NO.8, SEQ ID NO.13 and SEQ ID NO. 17.
The polypeptide with the amino acid sequence shown as SEQ ID NO.1 is 80 cyclic peptide obtained by detecting the change of the intracellular calcium ion concentration from a polypeptide library through a high-throughput screening technology, and the discovery of the cyclic peptide comprises the steps of cell culture process, cell plating, dissolution and dilution of the polypeptide library and detection of an MC3 receptor inhibitor; decompressing the 80-cyclic peptide to obtain small cyclic peptide and linear peptide with the amino acid sequences shown in SEQ ID NO. 2-18.
Wherein the polypeptide library is prepared by adopting PICT (Peptide Information Compression Technology) patent technology by SangZhonghua full peptide biochemical limited company in Hunan, and the technology compresses polypeptide information by utilizing biological means, so that the information of a plurality of polypeptides can be integrated into one polypeptide, and the aim of containing larger polypeptide information with relatively smaller library capacity is fulfilled; a cyclic peptide library containing approximately 73000 80 amino acids was constructed by the PICT technique.
Wherein, the first amino acid and the 80 th amino acid in the amino acid sequence shown in SEQ ID NO.1 are connected through peptide bonds to form a ring, so as to form a cyclic peptide; the first amino acid and 23 rd amino acid in the amino acid sequence shown in SEQ ID NO.7 are connected through peptide bonds to form a ring to form a cyclic peptide; the first amino acid and the 19 th amino acid in the amino acid sequence shown in SEQ ID NO.8 are connected to form a ring to form a cyclic peptide; the first amino acid and 18 th amino acid in the amino acid sequence shown in SEQ ID NO.9 are connected to form a ring to form a cyclic peptide; the first amino acid and the 17 th amino acid in the amino acid sequence shown in SEQ ID NO.10 are connected to form a ring to form a cyclic peptide; the first amino acid and the 16 th amino acid in the amino acid sequence shown in SEQ ID NO.11 are connected to form a ring to form a cyclic peptide; the first amino acid and the 15 th amino acid in the amino acid sequence shown in SEQ ID NO.12 are connected to form a ring to form a cyclic peptide; the first amino acid and the 14 th amino acid in the amino acid sequence shown in SEQ ID NO.13 are connected to form a ring to form a cyclic peptide; the first amino acid and the 13 th amino acid in the amino acid sequence shown in SEQ ID NO.14 are connected to form a ring to form a cyclic peptide; the first amino acid and the 12 th amino acid in the amino acid sequence shown in SEQ ID NO.15 are connected to form a ring to form a cyclic peptide; the first amino acid and the 11 th amino acid in the amino acid sequence shown in SEQ ID NO.16 are connected to form a ring to form a cyclic peptide; the first amino acid and the 10 th amino acid in the amino acid sequence shown in SEQ ID NO.17 are connected to form a ring to form a cyclic peptide; the first amino acid and the 9 th amino acid in the amino acid sequence shown in SEQ ID NO.18 are connected to form a ring to form a cyclic peptide; the amino acid sequence shown in any one of SEQ ID NO.2-6 is a linear peptide.
In order to solve the second technical problem, the invention discloses a nucleotide which codes for the polypeptide.
In order to solve the third technical problem, the invention discloses an MC3 receptor inhibitor, which comprises the polypeptide.
In order to solve the fourth technical problem, the invention discloses a pharmaceutical composition for preventing or treating metabolic diseases, wherein the active ingredients of the pharmaceutical composition comprise the polypeptide or the MC3 receptor inhibitor.
Wherein, the pharmaceutical composition also comprises a pharmaceutically acceptable carrier.
Wherein the metabolic disease includes, but is not limited to, obesity.
In order to solve the fifth technical problem, the invention discloses application of the polypeptide, or the MC3 receptor inhibitor, or the pharmaceutical composition in preparing medicines for preventing or treating metabolic diseases.
Wherein the metabolic disease includes, but is not limited to, obesity.
In order to solve the sixth technical problem, the invention discloses a medicament for preventing or treating metabolic diseases, wherein the active ingredients of the medicament comprise the polypeptide, or the MC3 receptor inhibitor, or the pharmaceutical composition.
Wherein the metabolic disease includes, but is not limited to, obesity.
The beneficial effects are that: compared with the prior art, the invention has the following advantages:
the invention applies high flux drug screening technology to screen the polypeptide named as 80 cyclic peptide 3 (PL 00803001) from a large cyclic peptide library, which can inhibit MC3 receptor and block activation of cell signal path. In addition, PL00803001 is a cyclic peptide containing 80 amino acids, and a series of derivative small cyclic peptides and linear peptides are obtained by decompression technology, and all have the function of an MC3 receptor inhibitor. PL00803001 and its series of polypeptides have very obvious inhibition effect on MC3 receptor, are MC3 receptor polypeptide inhibitors, and can be further developed into new polypeptide medicines for metabolic diseases including but not limited to obesity.
Drawings
The foregoing and/or other advantages of the invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings and detailed description.
FIG. 1 is a diagram showing the effect of the inhibition of MC3R cells by cyclopeptide 80 at a concentration of 2. Mu.M.
FIG. 2 is a concentration response curve of the inhibition of ACTH agonizing MC3R cells by the 80-cyclic peptide.
FIG. 3 is a raw graph of ACTH signal inhibition at various concentrations of linear peptide (PL 00803004) of 40 amino acids (10. Mu.M for PL00803004-1, 3-fold dilution to 8 th concentration in sequence).
FIG. 4 is a concentration response curve of a linear peptide of 40 amino acids in inhibiting ACTH agonizing MC3R cells.
FIG. 5 is a raw graph of ACTH signal inhibition at 23 amino acid number cyclic peptides (PL 00803083) at various concentrations (10. Mu.M for PL00803083-1, 3-fold dilution to 8 th concentration in sequence).
FIG. 6 is a concentration response curve of cyclic peptides of 23 amino acids (PL 00803083) inhibiting ACTH agonizing MC3R cells.
Fig. 7 is a raw graph of ACTH signal inhibition at a concentration of 0.37 μm for 19 amino acid number cyclic peptide (PL 00803107) and 14 amino acid number cyclic peptide (PL 00803112) and control SHU9119.
FIG. 8 is a concentration response curve of cyclic peptides of 13-19 amino acid numbers (PL 00803107 to PL 00803113) and control inhibitor SHU9119 inhibiting ACTH agonizing MC3R cells.
FIG. 9 is a raw graph of ACTH signal inhibition by cyclic peptides of 9 to 12 amino acid numbers (PL 00803134 to PL 00803137) at a concentration of 1.11. Mu.M.
Fig. 10 is a concentration response curve of cyclic peptides of 9 to 12 amino acid numbers (PL 00803134 to PL 00803137) inhibiting ACTH agonizing MC3R cells.
Detailed Description
The invention will be better understood from the following examples. However, it will be readily appreciated by those skilled in the art that the description of the embodiments is provided for illustration only and should not limit the invention as described in detail in the claims.
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials, unless otherwise specified, are commercially available.
Example 1:
1. key reagent: a polypeptide library (homemade), CHO cell (Chinese hamster ovary cell ) line overexpressing MC3R, abbreviated CHO-K1/MC3R/gα15 cells, calcium5 Assay Kit.
2. High throughput screening process
Culture of CHO-K1/MC 3R/G.alpha.15 cells
2.1.1. Cell resuscitation: the cells were removed from the liquid nitrogen tank and rapidly thawed in a 37 ℃ water bath. Cells were transferred to a 15mL centrifuge tube, 9mL of pre-warmed thawing medium was slowly added, centrifuged at 800 rpm for 5 minutes, and the supernatant medium was removed. The cells were resuspended in 5mL of thawing medium, transferred to T25 flasks, and placed at 37℃in 5% CO 2 Incubator of (a)Is cultured. The following day of cell resuscitation the medium was replaced with growth medium.
2.1.2. Cell passage: when the cells grow up to 80-90% of the culture flask, firstly, using DPBS to rinse the cells, and then using 0.25% pancreatin to digest the cells; collecting cell suspension into a centrifuge tube, centrifuging at 800 rpm for 5 minutes, and removing the supernatant medium; 6-8mL of fresh growth medium was added, cells were resuspended, and the ratio was 1:3-1:10, and then is placed at 37 ℃ and 5 percent CO 2 Is cultured in an incubator of (a). Liquid changes were performed every 2-3 days after passaging.
2.1.3. Cell cryopreservation: when the cells grow up to 80-90% of the culture dish, the cells are firstly rinsed by DPBS, and then the cells are digested by 0.25% pancreatin; collecting cell suspension into a centrifuge tube, centrifuging at 800 rpm for 5 minutes, and removing the supernatant medium; resuspension of cells with cryopreservation medium, cell counting, dilution of cells to 2-3X 10 6 /mL. Each cryopreservation tube was filled with 1mL of cell cryopreservation suspension. And (3) placing the frozen storage tube of the packaged cells into a frozen storage box, placing the frozen storage box into a refrigerator at the temperature of minus 80 ℃ for overnight storage, and transferring the frozen storage tube into a liquid nitrogen tank.
CHO-K1/MC 3R/G.alpha.15 cell plating
24 hours before testing, CHO-K1/MC3R/G alpha 15 cells in a culture flask are subjected to 0.25% pancreatin digestion treatment and suspended in a cell culture solution, and added into a 384-well plate with a black transparent bottom to be cultured at a density of 10000 cells per well by using a liquid separator, wherein 25 mu L per well, 37 ℃ and 5% CO are used for culturing 2 Culturing overnight.
2.3.Calcium5 assay kit working fluid preparation
On the day of the test, component A in the Calcium5 kit was dissolved in a Calcium dye buffer (Loading buffer) and 250mM probenecid was added to prepare a Calcium dye solution containing 5mM probenecid.
After the medium was aspirated, 50 μl of calcium dye solution was added to each well of the cell culture plate and left to incubate at room temperature for 2 hours.
2.4. Polypeptide pool dissolution and dilution
2.4.1. Polypeptide pool lysis
2.4.2. The polypeptide library 96-well deep well plate was placed in a centrifuge at 4000rpm for centrifugation for 2-3 minutes. 200. Mu.L/well of ultrapure water was added to the 96-well deep-well plate using an automatic liquid separator. Sealed with a silica gel cap and placed in a 95℃water bath for 5 minutes. And (3) injection: the polypeptide concentration at this time was about: 50. Mu.M.
2.4.3. The 96 deep-well plate polypeptides after dissolution were placed in a centrifuge at 4000rpm for centrifugation for 2-3 minutes.
2.5. Dilution of polypeptide pool
The polypeptide solution dissolved in the step 2.4 was transferred to a 384-well plate using a workstation, and diluted to 10. Mu.M with a loading buffer.
FLIPR assay
After 2 hours of addition of the Calcium5 dye, the cell culture plates were removed and left at room temperature for 10 minutes in the dark, and then placed in the FLIPR instrument with the polypeptide solution plates for detection. ACTH was set as an agonist positive control and SHU9119 was set as an inhibitor positive control.
3. Confirmation of different 80-cyclic peptides
3.1. The as-screened polypeptides were confirmed according to the procedure of step 2.
3.2. IC50 value of the active polypeptide was determined according to the procedure of step 2
On the day of detection, the active polypeptide mother liquor was diluted to 50. Mu.M (5 Xconcentration) with 1 Xloading buffer (pH: 7.4), diluted by a multiple ratio for 8-10 gradients, and each concentration was subjected to multiplex well to test the IC50 value of the active polypeptide.
4. Experimental results
4.1 from approximately 7.3 ten thousand 80 cyclic peptides, 5 polypeptides capable of inhibiting MC3 receptor activation at the cellular level were found by high throughput screening and a reconfirmation experiment was performed, as shown in FIG. 1, listing the original map of PL00803001 (i.e., 80 cyclic peptide 3, the amino acid sequence of which is shown in SEQ ID NO. 1).
4.2 after confirming the inhibitory effect of the 80-cyclopeptide, the concentration response curve of the inhibitory effect on the MC3 receptor was tested, and the IC50 value was as shown in FIG. 2, PL00803001 had the strongest inhibitory effect on the MC3 receptor, and the IC50 value was 0.23. Mu.M.
EXAMPLE 2 screening of derived peptides
Screening and confirmation of PL00803001 derived polypeptides
The internal decompression technology is applied to decompress the 80 cyclic peptide 3 (PL 00803001) to design cyclic peptides or linear peptides with 5-80 different amino acid sequences.
Screening was performed according to the screening procedure of step 2 in example 1 and IC50 validation was performed on the screened decompressed active polypeptide according to step 3.2 in example 1, as well as on the control inhibitor SHU9119.
2. Experimental results:
decompression screening was performed on the 80-cyclopeptide PL00803001 and the active polypeptides were validated against MC3 receptor inhibitory concentration response curves as shown in table 1, table 2 and figures 3 to 10. Wherein the IC50 value of the inhibition of MC3R receptor by PL00803107, PL00803112, PL00803136 is about 1-2 times lower than the IC50 value of the inhibition of MC3R receptor by control inhibitor SHU 9119; the discovered inhibition effect of the active polypeptide is superior to that of the existing control inhibitor SHU9119.
Table 1 IC50 values for the inhibition of MC3 receptors by the 40 amino acid linear peptides
TABLE 2 IC50 values for amino acid cyclic peptides inhibiting MC receptors
The invention provides a polypeptide for inhibiting MC3 receptor activation, and an application thought and a method thereof, and a method and a way for realizing the technical scheme are numerous, the above is only a preferred embodiment of the invention, and it should be noted that, for a person skilled in the art, several improvements and modifications can be made, and the improvements and modifications should be regarded as the protection scope of the invention, without departing from the principle of the invention. The components not explicitly described in this embodiment can be implemented by using the prior art.
Sequence listing
<110> Hunan Zhongcheng full peptide Biochemical Co., ltd
<120> a polypeptide inhibiting MC3 receptor activation and use thereof
<160> 18
<170> SIPOSequenceListing 1.0
<210> 1
<211> 80
<212> PRT
<213> PL00803001
<400> 1
His His His His Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser
1 5 10 15
Asn Ser Ala Lys Cys Leu Ser Leu Ser Pro Ala Ala Thr Thr Ser Pro
20 25 30
Ala Arg Arg Gly Trp Arg Cys Val Lys Arg Arg Trp Met Arg Arg Met
35 40 45
Ala Ser Asn Thr Ala Pro Trp Ser Pro Pro Trp Arg Val Thr Ala Ser
50 55 60
Ser Ser Ala Cys Gly Ser Ala Ala Cys Arg Gly Tyr Cys Phe His His
65 70 75 80
<210> 2
<211> 40
<212> PRT
<213> PL00803003
<400> 2
His His His His His His Arg Arg Gly Leu Phe Arg Arg Val Ile Pro
1 5 10 15
Ser Ser Asn Ser Ala Lys Cys Leu Ser Leu Ser Pro Ala Ala Thr Thr
20 25 30
Ser Pro Ala Arg Arg Gly Trp Arg
35 40
<210> 3
<211> 40
<212> PRT
<213> PL00803004
<400> 3
His His His His Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser
1 5 10 15
Asn Ser Ala Lys Cys Leu Ser Leu Ser Pro Ala Ala Thr Thr Ser Pro
20 25 30
Ala Arg Arg Gly Trp Arg Cys Val
35 40
<210> 4
<211> 40
<212> PRT
<213> PL00803006
<400> 4
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Ser Ala Lys
1 5 10 15
Cys Leu Ser Leu Ser Pro Ala Ala Thr Thr Ser Pro Ala Arg Arg Gly
20 25 30
Trp Arg Cys Val Lys Arg Arg Trp
35 40
<210> 5
<211> 40
<212> PRT
<213> PL00803037
<400> 5
Ala Cys Gly Ser Ala Ala Cys Arg Gly Tyr Cys Phe His His His His
1 5 10 15
His His Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Ser
20 25 30
Ala Lys Cys Leu Ser Leu Ser Pro
35 40
<210> 6
<211> 40
<212> PRT
<213> PL00803040
<400> 6
Cys Arg Gly Tyr Cys Phe His His His His His His Arg Arg Gly Leu
1 5 10 15
Phe Arg Arg Val Ile Pro Ser Ser Asn Ser Ala Lys Cys Leu Ser Leu
20 25 30
Ser Pro Ala Ala Thr Thr Ser Pro
35 40
<210> 7
<211> 23
<212> PRT
<213> PL00803083
<400> 7
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Ser Ala Lys
1 5 10 15
Cys Leu Ser Leu Trp Arg Ser
20
<210> 8
<211> 19
<212> PRT
<213> PL00803107
<400> 8
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Ser Ala Lys
1 5 10 15
Trp Arg Ser
<210> 9
<211> 18
<212> PRT
<213> PL00803108
<400> 9
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Ser Ala Trp
1 5 10 15
Arg Ser
<210> 10
<211> 17
<212> PRT
<213> PL00803109
<400> 10
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Ser Trp Arg
1 5 10 15
Ser
<210> 11
<211> 16
<212> PRT
<213> PL00803110
<400> 11
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Asn Trp Arg Ser
1 5 10 15
<210> 12
<211> 15
<212> PRT
<213> PL00803111
<400> 12
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Ser Trp Arg Ser
1 5 10 15
<210> 13
<211> 14
<212> PRT
<213> PL00803112
<400> 13
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Ser Trp Arg Ser
1 5 10
<210> 14
<211> 13
<212> PRT
<213> PL00803113
<400> 14
Arg Arg Gly Leu Phe Arg Arg Val Ile Pro Trp Arg Ser
1 5 10
<210> 15
<211> 12
<212> PRT
<213> PL00803134
<400> 15
Arg Arg Gly Leu Phe Arg Arg Val Ile Trp Arg Ser
1 5 10
<210> 16
<211> 11
<212> PRT
<213> PL00803135
<400> 16
Arg Arg Gly Leu Phe Arg Arg Val Trp Arg Ser
1 5 10
<210> 17
<211> 10
<212> PRT
<213> PL00803136
<400> 17
Arg Arg Gly Leu Phe Arg Arg Trp Arg Ser
1 5 10
<210> 18
<211> 9
<212> PRT
<213> PL00803137
<400> 18
Arg Arg Gly Leu Phe Arg Trp Arg Ser
1 5
Claims (9)
1. A polypeptide, characterized in that the first amino acid and the 80 th amino acid in the amino acid sequence shown in SEQ ID No.1 are linked to form a cyclic peptide; or the first amino acid and the 19 th amino acid in the amino acid sequence shown in SEQ ID NO.8 are connected to form a ring to form a cyclic peptide; or the first amino acid and the 14 th amino acid in the amino acid sequence shown in SEQ ID NO.13 are connected to form a ring to form a cyclic peptide; or the first amino acid and the 10 th amino acid in the amino acid sequence shown in SEQ ID NO.17 are connected to form a ring to form a cyclic peptide.
2. A nucleotide encoding the polypeptide of claim 1.
3. An inhibitor of the MC3 receptor comprising the polypeptide of claim 1.
4. A pharmaceutical composition for preventing or treating metabolic diseases, wherein the active ingredient of the pharmaceutical composition comprises the polypeptide of claim 1, or the MC3 receptor inhibitor of claim 3.
5. The pharmaceutical composition of claim 4, further comprising a pharmaceutically acceptable carrier.
6. The pharmaceutical composition of claim 4, wherein the metabolic disorder is obesity.
7. Use of the polypeptide of claim 1, or the MC3 receptor inhibitor of claim 3, or the pharmaceutical composition of any one of claims 4-6, in the manufacture of a medicament for the prevention or treatment of a metabolic disease.
8. The use according to claim 7, wherein the metabolic disease is obesity.
9. A medicament for preventing or treating metabolic diseases, characterized in that the active ingredient of the medicament comprises the polypeptide of claim 1, or the MC3 receptor inhibitor of claim 3, or the pharmaceutical composition of any one of claims 4 to 6.
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