CN113461785A - GLP-1 receptor agonists and uses thereof - Google Patents
GLP-1 receptor agonists and uses thereof Download PDFInfo
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- CN113461785A CN113461785A CN202110392318.9A CN202110392318A CN113461785A CN 113461785 A CN113461785 A CN 113461785A CN 202110392318 A CN202110392318 A CN 202110392318A CN 113461785 A CN113461785 A CN 113461785A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention discloses a GLP-1 receptor agonist, belonging to the field of biological medicines. The invention applies high-flux drug screening technology to screen polypeptide named 100-44(PL00201001) from a large cyclic peptide library, and the polypeptide can activate GLP-1 receptor to cause the activation of cell signaling pathway. PL00201001 contains a cyclic peptide of 80 amino acids, and a series of derived small cyclic peptides and linear peptides obtained by decompression technique, both having GLP-1 receptor agonist effect. PL00201001 and a series of polypeptides thereof can be used as GLP-1 receptor agonist, and can be used for further developing new polypeptide drugs for diabetes, obesity and related diseases.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to a GLP-1 receptor agonist and application thereof.
Background
Protein-coupled receptors (GPCRs) are a class of 7-transmembrane receptors, which belong to cell membrane surface receptors and account for approximately 4% of the proteins encoded by the human genome. There are about 475 FDA-approved drug targets, with about 108 GPCRs, accounting for 34%. The global sales of GPCRs receptor drugs exceeds 1800 billion dollars each year, which accounts for more than 27% of the global drug market, and therefore, the development of the GPCRs receptor drugs has wide prospects.
Glucagon-like peptide-1 receptor (GLP-1R) is a class B GPCRs consisting of 463 amino acids. The GLP-1R is affected by endogenous GLP-1 polypeptides including (GLP-1(1-36) NH2GLP-1 (7-36) NH2, GLP-1(1-37) and GLP-1(7-37) and exogenous polypeptide exendin-4.
Glucagon-like peptide-1 (1-37) (GLP-1), a polypeptide consisting of 37 amino acids with the amino acid sequence of HDEFERHAEGTFTSDVSSYLEGQAAKEFI AWLVKGRG, is a polypeptide hormone secreted by ileum endocrine cells, and can regulate insulin secretion, inhibit glucagon secretion, delay gastrointestinal tract emptying and inhibit appetite by acting on GLP-1 receptor, thereby achieving the purpose of controlling sugar intake and further regulating blood sugar concentration.
The GLP-1 receptor agonist drugs which are currently marketed comprise exenatide, lixisenatide, liraglutide, albiglutide, dolabrlutide and somaglutide, and the drugs are a series of GLP-1 analogue drugs which are developed on the basis of GLP-1 sequences. The market size of global GLP-1 receptor agonists in 2018 is about $ 88.27 billion, and still continues to grow faster.
The molecular weight of the polypeptide drug is between that of a small molecule drug and a biological product, and the polypeptide drug has unique characteristics, because the polypeptide is used as a signal molecule in a body to participate in a plurality of physiological functions, the polypeptide drug is often used as a replacement therapy to compensate for the lack of endogenous polypeptide hormone level, in 2019, the polypeptide drug accounts for 5 percent of the global medicine market, and the global sales amount exceeds 500 hundred million dollars.
The existing GLP-1 receptor agonists are all reconstructed based on endogenous GLP-1 sequences, and at present, the agonists have no brand new polypeptide sequences, are all linear GLP-1 analogues, are easy to degrade in vivo and have short half-life. The invention discovers that the polypeptide of the GLP-1 receptor agonist with the brand-new sequence still has higher activity under the condition of cyclization, and the half-life period of the polypeptide in vivo can be predicted to be improved.
The polypeptide medicament is mainly modified on the basis of natural active polypeptide, and the invention applies a large-scale polypeptide library with independent intellectual property rights and adopts a high-throughput screening technology to obtain the GLP-1 receptor agonist with the serial number of PL00201001 polypeptide and serial linear and cyclic polypeptides with different amino acid numbers.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to solve the technical problem of providing a GLP-1 receptor agonist and application thereof.
In order to solve the technical problems, the invention adopts the following technical scheme:
the GLP-1 receptor agonist has an amino acid sequence shown as SEQ ID No. 1-6.
Wherein, the 1 st amino acid and the 80 th amino acid of the amino acid sequence shown in SEQ ID NO.1 are connected through a peptide bond to form a protein which is a cyclic peptide;
the protein formed by the amino acid sequence shown in SEQ ID NO.2 is a linear peptide;
The 1 st amino acid and the 58 th amino acid of the amino acid sequence shown in SEQ ID NO.3 are connected through a peptide bond to form a protein which is cyclic peptide;
the protein formed by the amino acid sequence shown in SEQ ID NO.4 is a linear peptide;
the 1 st amino acid and the 43 th amino acid of the amino acid sequence shown in SEQ ID NO.5 are connected through a peptide bond to form a protein which is cyclic peptide;
the 1 st amino acid and the 17 th amino acid of the amino acid sequence shown in SEQ ID NO.6 are connected through a peptide bond to form a protein which is a cyclic peptide.
The GLP-1 receptor stimulant is applied to the preparation of medicines for treating diabetes and obesity.
A pharmaceutical composition comprising the GLP-1 receptor agonist of claim 1 or a pharmaceutically acceptable carrier thereof.
The amino acid sequence of 80 cyclic peptide and linear and cyclic peptides with different amino acid numbers in series and the application thereof as GLP-1 receptor agonist medicine are screened from a large polypeptide library by adopting a method for detecting the concentration of calcium ions in cells.
The GLP-1 receptor stimulant PL 0020100180 amino acid cyclic peptide provided by the invention is 80 cyclic peptide obtained by detecting the concentration change of calcium ions in cells from an independent intellectual property polypeptide library through a high-throughput screening technology, and a series of decompressed small cyclic peptides and linear peptides.
The discovery of the PL00201001 polypeptide involves cell culture processes, cell plating, solubilization and dilution of the polypeptide library, and detection of GLP-1 receptor agonism.
Has the advantages that:
the invention discloses a GLP-1 receptor agonist PL00201001 polypeptide and series of decompressed polypeptides, which have very obvious agonistic effect on a GLP-1 receptor and are GLP-1 receptor agonists.
Drawings
FIG. 1: the effect of PL00201001 on agonism of GLP-1R receptor was confirmed.
FIG. 2: PL00201001 agonizes GLP-1 receptor concentration response curves.
FIG. 3: PL00201001 corresponds to the effect of a linear peptide of 80 amino acids (PL00201245) on the GLP-1R receptor.
FIG. 4: decompression of PL00201001 resulted in the action of a 58 amino acid numbered cyclic peptide (PL00201063) on the GLP-1R receptor.
FIG. 5: decompression of PL00201001 resulted in the action of a 48 amino acid number linear peptide (PL00201071) on the GLP-1R receptor.
FIG. 6: decompression of PL00201001 resulted in the action of a 43 amino acid number of cyclic peptide (PL00201050) on the GLP-1R receptor.
FIG. 7: PL00201050, PL00201063, PL00201071, PL00201245, PL002011372 activate GLP-1 receptor concentration response curve.
Detailed Description
The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only for illustrating the present invention and should not be taken as limiting the invention as detailed in the claims.
Example 1:
1. key reagents: polypeptide library (homemade), CHO cell over-expressing GLP-1R (Chinese hamster ovary cell) line, abbreviated CHO-K1/GLP-1R/G alpha 15 cell (Genscript), Calcium 6Assay Kit (Molecular Devices).
2. High throughput screening process
Culture of CHO-K1/GLP 1/G.alpha.15 cells
2.1.1. Cell recovery: the cells were removed from the liquid nitrogen tank and quickly thawed in a 37 ℃ water bath. The 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 thawed medium, transferred to a T25 flask and incubated at 37 ℃ in a 5% CO2 incubator. And (5) the cells are recovered for the next day, and the culture solution is replaced into a growth culture medium.
2.1.2. Cell passage: when the cells grow to be full of the culture bottle by 80-90%, the cells are firstly rinsed by DPBS, and then 0.25% pancreatin is used for digesting the cells; collecting the cell suspension into a centrifuge tube, centrifuging for 5 minutes at 800 revolutions, and removing a supernatant culture medium; add 6-8mL of fresh growth medium, resuspend cells, 1: 3-1: the 10 lines were passaged and cultured at 37 ℃ in a 5% CO2 incubator. The liquid change is carried out every 2-3 days after passage.
2.1.3. Freezing and storing cells: when the cells grow to be 80-90% full of the culture dish, firstly rinsing the cells by using DPBS (deep plasma-assisted plasma) and then digesting the cells by using 0.25% of pancreatin; collecting the cell suspension into a centrifuge tube, centrifuging for 5 minutes at 800 revolutions, and removing a supernatant culture medium; resuspending the cells in a cryopreservation medium, counting the cells, and diluting the cells to 2-3X 106/mL. Each vial was filled with 1mL of cell cryopreservation suspension. And (3) putting the freezing tube with the subpackaged cells into a freezing box, putting the freezing box into a refrigerator at the temperature of-80 ℃ for overnight preservation, and transferring the freezing tube into a liquid nitrogen tank.
CHO-K1/GLP 1/G.alpha.15 cell plating
24 hours before the test, CHO-K1/GLP 1/G.alpha.15 cells in a culture flask were subjected to 0.25% trypsin digestion and suspended in a cell culture solution, and cultured in a 384-well black transparent bottom plate at a density of 10000 cells per well using a liquid separator, 25. mu.l per well, 37 ℃, 5% CO2The culture was carried out overnight.
Preparation of Calcum 6assay kit for working solution
On the day of testing, component a in the Calcium 6 kit was dissolved in Calcium dye buffer (Loading buffer) and 250mM probenecid was added to make a Calcium dye solution containing 5mM probenecid.
Mu.l of calcium dye solution was added to each well of the cell culture plate, and the plate was incubated at 37 ℃ and 5% CO2 for 2 hours.
2.4. Polypeptide library solubilization and dilution
2.4.1. Polypeptide library solubilization
2.4.2. And placing the 96-hole deep-hole plate of the polypeptide library in a centrifuge for centrifuging for 2-3 minutes at 4000 rpm. 250 μ L/well of ultrapure water was added to a 96-well deep-well plate using an automatic liquid separator 5.1.2. The mixture was sealed with a silica gel cap and left in a water bath at 95 ℃ for 5 minutes. Note: the polypeptide concentration is then about: 200 μ M.
2.4.3. And (4) placing the dissolved 96 deep-hole plate polypeptide in a centrifuge for 2-3 minutes at 4000 rpm.
2.5. Polypeptide library dilution
The dissolved sample was transferred to a 384-well plate using a workstation and diluted to 10uM with a loading buffer.
FLIPR detection
After 2 hours of cell addition with Calcium 6 dye, the cell culture plates were removed and placed at room temperature in the dark for 10 minutes, and then placed with the polypeptide solution plate into the FLIPR instrument for detection. GLP-1 was set as a positive control.
PL00201001 validation
3.1. The primary screened polypeptides were confirmed according to the procedure of step 2.
3.2. Detection of the EC50 value of the active polypeptide according to the procedure of step 2
On the day of the assay, the active polypeptide stock solution was diluted to 50. mu.M (5 Xconcentration) with 1 Xloading buffer (containing 20mM HEPES) (pH:7.4) and further diluted 3-fold in 8 gradients with 3 duplicate wells per concentration to test the EC50 value for the active polypeptide.
Screening and validation of PL 00201001-derived Polypeptides
Decompressing amino acids of 80-cyclopeptide PL00201001 to design cyclic peptides or linear peptides with different amino acid sequences of 10-80.
The polypeptide sequence obtained by the invention is as follows:
SEQ ID NO.1
PL 00201001: the 1 st and 80 th amino acids are cyclized by peptide bond
HHHHHHFIHECFVRCCWTKWHRPNCNTESQCVWWFHCIWAAHKEHDAN HKQCQDKDEPYEQQHHKWKMFLLYMIAFLYCL
SEQ ID NO.2
PL 00201245: PL00201001 linear peptide
HHHHHHFIHECFVRCCWTKWHRPNCNTESQCVWWFHCIWAAHKEHDAN HKQCQDKDEPYEQQHHKWKMFLLYMIAFLYCL
SEQ ID NO.3
PL 00201063: the 1 st and 58 th amino acids are cyclized by peptide bond
RCCWTKWHRPNCNTESQCVWWFHCIWAAHKEHDANHKQCQDKDEPYE QQHHKWKMFLL
SEQ ID NO.4
PL 00201071: linear peptide of 48 amino acids
CWTKWHRPNCNTESQCVWWFHCIWAAHKEHDANHKQCQDKDEPYEQQ H
SEQ ID NO.5
PL 00201050: the 1 st and 43 th amino acids are cyclized by peptide bond
CWTKWHRPNCNTESQCVWWFHCIWAAHKEHDANHKQCQDKDEP
SEQ ID NO.6
PL 00201372: the 1 st and 17 th amino acids are cyclized by peptide bond
FHCIWAAHKEHDANHKQC
Screening was performed according to the step 2 screening procedure and EC50 validation was performed on the screened, decompressed active polypeptides according to step 3.2.
5. The experimental results are as follows:
1. by high throughput screening, PL00201001 numbered polypeptide was found from nearly 8 thousand 80-loop peptides, able to agonize the GLP-1R receptor at the cellular level, and the experiments were reconfirmed, as shown in figure 1.
2. After confirming PL00201001 agonism, a response curve of PL00201001 to GLP-1R receptor concentration was performed, resulting in an EC50 value of 0.6 μ M, as shown in fig. 2.
3. Decompression screening was performed on 80-cyclic peptide PL00201001, and the results are shown in fig. 3 to 6.
4. After decompression of 80-cyclopeptide PL00201001, the active polypeptide was validated against the GLP-1R receptor concentration response curve, as shown in FIG. 7.
Sequence listing
<110> Cheng quan peptide Biochemical Co., Ltd in Hunan province
<120> GLP-1 receptor agonists and uses thereof
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Gln Cys
Claims (10)
- The GLP-1 receptor agonist is characterized in that the amino acid sequence of the GLP-1 receptor agonist is shown as SEQ ID No. 1-6.
- 2. The GLP-1 receptor agonist according to claim 1, wherein the 1 st amino acid and the 80 th amino acid of the amino acid sequence represented by SEQ ID No.1 are linked by a peptide bond to form a protein as a cyclic peptide.
- 3. The GLP-1 receptor agonist according to claim 1, wherein the protein formed by the amino acid sequence represented by SEQ ID No.2 is a linear peptide.
- 4. The GLP-1 receptor agonist according to claim 1, wherein the 1 st amino acid and the 58 th amino acid of the amino acid sequence represented by SEQ ID No.3 are linked by a peptide bond to form a protein as a cyclic peptide.
- 5. The GLP-1 receptor agonist according to claim 1, wherein the protein formed by the amino acid sequence shown in SEQ ID No.4 is a linear peptide.
- 6. The GLP-1 receptor agonist according to claim 1, wherein the 1 st amino acid and the 43 th amino acid of the amino acid sequence represented by SEQ ID No.5 are linked by a peptide bond to form a protein as a cyclic peptide.
- 7. The GLP-1 receptor agonist according to claim 1, wherein the 1 st amino acid and the 17 th amino acid of the amino acid sequence represented by SEQ ID No.6 are linked by a peptide bond to form a protein as a cyclic peptide.
- 8. Use of a GLP-1 receptor agonist according to any one of claims 1 to 7 for the preparation of a medicament for the treatment of diabetes.
- 9. Use of a GLP-1 receptor agonist of any one of claims 1 to 7 in the preparation of a medicament for the treatment of obesity.
- 10. A pharmaceutical composition comprising a GLP-1 receptor agonist according to any one of claims 1 to 2 or a pharmaceutically acceptable carrier thereof.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114788876A (en) * | 2022-02-24 | 2022-07-26 | 北京医院 | mRNA medicinal preparation for treating diabetes, preparation method and application thereof |
CN115043910A (en) * | 2022-03-25 | 2022-09-13 | 湖南中晟全肽生化有限公司 | Polypeptide for inhibiting TIGIT and CD155 combination and application thereof |
CN116751261A (en) * | 2023-06-29 | 2023-09-15 | 湖南中晟全肽生化有限公司 | GALR2 agonist and application thereof |
CN116751261B (en) * | 2023-06-29 | 2024-05-14 | 湖南中晟全肽生物科技股份有限公司 | GALR2 agonist and application thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003040309A2 (en) * | 2001-10-05 | 2003-05-15 | Bayer Pharmaceuticals Corporation | Peptides acting as both glp-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use |
WO2006121860A2 (en) * | 2005-05-06 | 2006-11-16 | Bayer Pharmaceuticals Corporation | Glucagon-like peptide 1 (glp-1) receptor agonists and their pharmacological methods of use |
CN111108117A (en) * | 2017-09-22 | 2020-05-05 | 瑞泽恩制药公司 | Glucagon-like peptide 1 receptor agonists and uses thereof |
-
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- 2021-04-13 CN CN202110392318.9A patent/CN113461785B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003040309A2 (en) * | 2001-10-05 | 2003-05-15 | Bayer Pharmaceuticals Corporation | Peptides acting as both glp-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use |
CN1564828A (en) * | 2001-10-05 | 2005-01-12 | 拜尔药品公司 | Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use |
WO2006121860A2 (en) * | 2005-05-06 | 2006-11-16 | Bayer Pharmaceuticals Corporation | Glucagon-like peptide 1 (glp-1) receptor agonists and their pharmacological methods of use |
CN111108117A (en) * | 2017-09-22 | 2020-05-05 | 瑞泽恩制药公司 | Glucagon-like peptide 1 receptor agonists and uses thereof |
Non-Patent Citations (1)
Title |
---|
BO AHREN: "Glucagon-like peptide-1 receptor agonists for type 2 diabetes: A rational drug development", 《JOURNAL OF DIABETES INVESTIGATION》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114788876A (en) * | 2022-02-24 | 2022-07-26 | 北京医院 | mRNA medicinal preparation for treating diabetes, preparation method and application thereof |
CN115043910A (en) * | 2022-03-25 | 2022-09-13 | 湖南中晟全肽生化有限公司 | Polypeptide for inhibiting TIGIT and CD155 combination and application thereof |
CN115043910B (en) * | 2022-03-25 | 2023-04-07 | 湖南中晟全肽生化有限公司 | Polypeptide for inhibiting TIGIT and CD155 combination and application thereof |
CN116751261A (en) * | 2023-06-29 | 2023-09-15 | 湖南中晟全肽生化有限公司 | GALR2 agonist and application thereof |
CN116751261B (en) * | 2023-06-29 | 2024-05-14 | 湖南中晟全肽生物科技股份有限公司 | GALR2 agonist and application thereof |
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