CN117586346A - Small molecule polypeptide and application thereof in preparation of psoriasis treatment drugs - Google Patents
Small molecule polypeptide and application thereof in preparation of psoriasis treatment drugs Download PDFInfo
- Publication number
- CN117586346A CN117586346A CN202311478323.7A CN202311478323A CN117586346A CN 117586346 A CN117586346 A CN 117586346A CN 202311478323 A CN202311478323 A CN 202311478323A CN 117586346 A CN117586346 A CN 117586346A
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- Prior art keywords
- small molecule
- psoriasis
- molecule polypeptide
- polypeptide
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- 229920001184 polypeptide Polymers 0.000 title claims abstract description 37
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 37
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 37
- 201000004681 Psoriasis Diseases 0.000 title claims abstract description 29
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 150000003384 small molecules Chemical class 0.000 title claims description 25
- 229940079593 drug Drugs 0.000 title description 11
- 238000002360 preparation method Methods 0.000 title description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 210000002510 keratinocyte Anatomy 0.000 abstract description 7
- 230000035755 proliferation Effects 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 8
- 229960002751 imiquimod Drugs 0.000 description 5
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 5
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 4
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 4
- 206010015150 Erythema Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 238000010587 phase diagram Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000000038 Hypoparathyroidism Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000669298 Pseudaulacaspis pentagona Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000013800 negative regulation of keratinocyte differentiation Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000013309 psoriasis mouse model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses a small molecular polypeptide and application thereof in preparing a medicament for treating psoriasis, wherein the amino acid sequence of the small molecular polypeptide is WYWHF, and the small molecular polypeptide is used for preparing the medicament for treating psoriasis by inhibiting proliferation of keratinocytes.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a small molecule polypeptide and application thereof in preparing a medicament for treating psoriasis.
Background
Psoriasis (Psoriasis) is a chronic skin disease characterized mainly by scaly skin lesions, which is caused by skin metabolic disorders, and is preferably caused by limbs, scalp and back. The clinical characteristics of the drug are as follows: red pimples or plaques, localized damaged surfaces are covered with silvery white scales, and the scales shed off by gentle scratching are thick and white, and are therefore called psoriasis.
Previous studies have shown that keratinocytes play an important role in the development of psoriasis, the pathological changes of which are highly abnormal proliferation of keratinocytes, hypoparathyroidism, thickening of acantha, infiltration of inflammatory cells and vascular proliferation. Therefore, inhibition of keratinocyte differentiation and proliferation and reduction of inflammatory infiltration are promising as one of the therapeutic approaches for psoriasis. The existing common psoriasis treatment methods comprise external medicines such as glucocorticoid, tretinoin and the like, or systemic treatment medicines, physical therapy and the like, but the method has poor effect, can only act on single pathological changes of psoriasis and has serious damage to liver, kidney and function-free bodies, so that a novel method for treating psoriasis is invented, a novel approach is provided for a treatment scheme of patients with psoriasis, and the conventional technology is broken through to develop a novel treatment scheme of psoriasis.
Disclosure of Invention
Therefore, the invention aims to provide a small molecular polypeptide and application thereof in preparing medicaments for treating psoriasis, and the psoriasis is treated by preparing a novel small molecular polypeptide.
The invention solves the technical problems by the following technical means:
a small molecule polypeptide has an amino acid sequence shown in SEQ ID NO.1, and a specific sequence is WYWHF (Trp-Tyr-Trp-His-Phe).
Further, the small molecule polypeptide has the following structural formula:
the invention relates to application of a small molecule polypeptide in preparing a medicament for treating psoriasis.
Further, the small molecule polypeptide is used at a concentration of 4-100. Mu. Mol/L.
Further, the small molecule polypeptides are used in combination with pharmaceutically acceptable carriers or excipients.
The beneficial effects are that:
the invention inhibits the proliferation of keratinocytes through the small molecular polypeptide WYWHF, reduces or inhibits the occurrence of red plaques and thick scales of skin, thereby treating psoriasis. Meanwhile, the small molecular polypeptide prepared by the invention can be prepared into ointment, and is convenient to use.
Drawings
FIG. 1 is a structural formula of a small molecule polypeptide;
FIG. 2 is a liquid phase diagram of a small molecule polypeptide;
FIG. 3 is a mass spectrum of a small molecule polypeptide;
FIG. 4 is a graph showing the effect of CCK8 detection of drug candidate WYWHF on HaCat cell proliferation;
fig. 5 is a psoriasis-like phenotype of the mice of example 2 negative, positive and test groups (WYWHF).
Detailed Description
The invention will be described in detail below with reference to specific embodiments and accompanying drawings:
example 1: experiment for inhibiting HaCat cell proliferation by small molecule polypeptide
(1) Cell sample preparation: inoculating HaCat (stored in dermatology laboratory of Beijing hospital) into 96-well plate with 6000 cells per well, 5 multiple wells per group, and placing in a solution containing 5% CO 2 The conventional culture in a incubator at 37 ℃ is added with the small molecule polypeptide disclosed by the invention for corresponding stimulation, wherein the amino acid sequence of the small molecule polypeptide is shown as SEQ ID NO.1, and SEQ ID NO.1: WYWHF (Trp-Tyr-Trp-His-Phe) is synthesized by the division of biological engineering (Shanghai) and has a structural formula shown in figure 1, and a liquid phase diagram and a mass spectrum shown in figures 2 and 3.
Wherein the drug concentration of the small molecule polypeptide used in the stimulation process is respectively 4 mu mol/L, 20 mu mol/L and 100 mu mol/L, and the small molecule polypeptide is treated for 0, 24h and 48h respectively, and the negative control group is not dosed.
(2) CCK8 staining and detection: when the cell stimulation reaches the corresponding time point, preparing 10% of CCK8 detection liquid by using a keratinocyte DMEM culture medium, discarding the original culture liquid in a 96-well plate, adding 100ul of CCK8 detection liquid into each well, incubating for 1h at 37 ℃, and detecting the absorbance at 450nm of each well by using a full-automatic enzyme-linked immunosorbent assay (ELISA), wherein the obtained data are shown in FIG. 4, and analyzing the data in FIG. 4 can be known:
compared with a control group, after the small molecular polypeptide WYWHF is treated for 24 hours, the cell proliferation rate is reduced, and especially at 48 hours, the small molecular polypeptide WYWHF can obviously inhibit the proliferation of keratinocytes in the concentration of 100 mu mol/L, so that the small molecular polypeptide disclosed by the invention can inhibit the proliferation of keratinocytes and further treat psoriasis.
Example 2: mouse experiment
1. The C57 male mice selected in the experiment are purchased from an experimental animal center of the medical university of air force and are fed in an SPF-class barrier environment of the center.
2. Negative group: imiquimod cream (IMQ);
positive group: the vitamin mod and imiquimod emulsifiable paste;
experimental group: small molecule polypeptide wywhf+imiquimod cream;
3. the backs of the C57 mice of each group were shaved and then given two days, once a day, the positive group was coated with this vitamin mod, the test group was coated with the small molecule polypeptide WYWHF, and the dose was 20ug/g. The imiquimod cream was then applied to the backs of mice at noon once a day for five consecutive days, 80 mg/day, to prepare an imiquimod-induced psoriasis mouse model, while continuing the drug treatment at noon for a total of 7 days. The obtained photographs were taken to observe the skin erythema and scaling of mice, and the results obtained are shown in fig. 5, and the results of fig. 5 were analyzed to see that:
after the IMQ-induced psoriasis mice are externally coated with the medicine for 7 days, the psoriasis-like phenotype change of the model mice is observed first, and the comparison shows that the IMQ-induced model mice have obviously increased back erythema and scales and obviously thickened epidermis and present the psoriasis-like phenotype. The mice which are simultaneously subjected to external smearing treatment of the vermod and the candidate drug WYWHF have the advantages that the back erythema is diluted, the scales are reduced, the psoriasis-like phenotype of model mice is obviously improved, and the improvement of the candidate polypeptide drug WYWHF group mice is most obvious, so that the external candidate polypeptide drug WYWHF can be used for relieving the psoriasis-like phenotype of model mice induced by IMQ, and further, the psoriasis is treated.
The above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the scope of the claims of the present invention. The technology, shape, and construction parts of the present invention, which are not described in detail, are known in the art.
Claims (4)
1. The small molecule polypeptide is characterized in that the amino acid sequence of the small molecule polypeptide is shown as SEQ ID NO. 1.
2. The small molecule polypeptide of claim 1, wherein the small molecule polypeptide has the structural formula:
3. use of a small molecule polypeptide according to claim 1 in the manufacture of a medicament for the treatment of psoriasis.
4. The use of a small molecule polypeptide according to claim 1 in the manufacture of a medicament for the treatment of psoriasis, wherein the small molecule polypeptide is used in combination with a pharmaceutically acceptable carrier or adjuvant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311478323.7A CN117586346A (en) | 2023-11-08 | 2023-11-08 | Small molecule polypeptide and application thereof in preparation of psoriasis treatment drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311478323.7A CN117586346A (en) | 2023-11-08 | 2023-11-08 | Small molecule polypeptide and application thereof in preparation of psoriasis treatment drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117586346A true CN117586346A (en) | 2024-02-23 |
Family
ID=89919211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311478323.7A Pending CN117586346A (en) | 2023-11-08 | 2023-11-08 | Small molecule polypeptide and application thereof in preparation of psoriasis treatment drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117586346A (en) |
-
2023
- 2023-11-08 CN CN202311478323.7A patent/CN117586346A/en active Pending
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| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
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