CN113248564A - Active peptide having tyrosinase inhibitory activity - Google Patents
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 51
- 102000003425 Tyrosinase Human genes 0.000 title claims abstract description 50
- 108060008724 Tyrosinase Proteins 0.000 title claims abstract description 50
- 230000002401 inhibitory effect Effects 0.000 title abstract description 16
- 230000000694 effects Effects 0.000 claims abstract description 20
- 230000005764 inhibitory process Effects 0.000 claims abstract description 12
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 claims abstract description 4
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- VNXWANZMRATDQM-UHFFFAOYSA-N 2-(2-phenylethyl)benzene-1,3-diol Chemical compound OC1=CC=CC(O)=C1CCC1=CC=CC=C1 VNXWANZMRATDQM-UHFFFAOYSA-N 0.000 description 2
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- AHMIDUVKSGCHAU-UHFFFAOYSA-N Dopaquinone Natural products OC(=O)C(N)CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-UHFFFAOYSA-N 0.000 description 1
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P17/00—Drugs for dermatological disorders
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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Abstract
The invention discloses an active peptide with tyrosinase inhibition effect, and the amino acid sequences of the active peptide are Ser-Asp-Trp (SDW), Gly-Ala-Arg (GAR) and Asp-Gly-Leu (DGL). The active peptide with the tyrosinase inhibiting effect can continuously and stably inhibit the activity of tyrosinase and inhibit the synthesis of melanin, has the advantages of high activity, safety, no toxicity, easy digestion and absorption and the like, can be used as a whitening functional component for cosmetics and health-care products which are beneficial to improving the chloasma function, and has wide application prospect and very important significance.
Description
Technical Field
The invention belongs to the field of bioactive peptides, and particularly relates to a bioactive peptide with tyrosinase inhibition effect.
Background
Tyrosinase (ec1.14.18.1), also known as polyphenol oxidase, is a key rate-limiting enzyme that catalyzes melanin synthesis, which is widely present in the body. During melanin production, tyrosinase catalyzes the oxidation of L-tyrosine to L-dopa, which is subsequently oxidized to L-dopaquinone, which is then converted to melanin by a series of non-enzymatic reactions. In the human body, tyrosinase is overexpressed, which may cause pigmentation diseases such as age spots, freckles, chloasma, melanoma, and the like. Among them, chloasma is the most common pigmentation disease, often occurs on female face, and seriously affects appearance. At present, no effective means for treating chloasma exists, emotional problems and psychological stress are caused to patients, and the quality of life is reduced. Meanwhile, tyrosinase activity has been found to be associated with parkinson's disease and other neurodegenerative diseases in the mammalian brain.
Researches find that the generation of skin melanin can be reduced by inhibiting the activity of tyrosinase, and the tyrosinase inhibitor has wide application prospects in the fields of cosmetics, health-care products and medicines. At present, common tyrosinase inhibitors mainly comprise kojic acid, ascorbic acid, arbutin and the like. The whitening cosmetic containing the tyrosinase inhibitor has a whitening effect on skin and can cause certain damage to the skin, and the inhibitor is easy to cause product instability. For example, kojic acid is widely used for treating melanodermopathy, but it has poor stability and can cause skin cancer in long-term use. Ascorbic acid is a widely used skin whitening agent, but fails to work rapidly by undergoing redox reactions. Arbutin has high photosensitivity and instability, and is easy to discolor when added into whitening cosmetics. The Chinese invention patent discloses a composition with a synergistic tyrosinase inhibition effect and an application (publication No. CN 111920790A, application date 2020.09.15), wherein the composition with the synergistic tyrosinase inhibition effect takes phenethyl resorcinol as an effective component, and the skin is affected by the use of the phenethyl resorcinol in an overdose manner. Therefore, the search for a novel tyrosinase inhibitor which is natural, nontoxic, stable and efficient is of great significance. The active peptide is natural, safe, efficient and easy to be absorbed by human body, and has good skin whitening effect.
The invention aims to provide an active peptide with tyrosinase inhibition effect, and the active peptide is applied to the preparation of health care products and whitening cosmetics which are helpful for improving chloasma.
Disclosure of Invention
The invention discloses an active peptide with tyrosinase inhibition effect, and the amino acid sequences of the active peptide are Ser-Asp-Trp, Gly-Ala-Arg and Asp-Gly-Leu respectively.
The active peptide with tyrosinase inhibition effect can be used for preparing health care products and whitening cosmetics which are helpful for improving chloasma.
The active peptide with tyrosinase inhibition effect has the butt-joint energy values of-84.32, -81.67, -112.12kcal mol-1semi-Inhibitory Concentration (IC) on tyrosinase Activity50) 0.84mg/mL, 0.34mg/mL, and 0.15mg/mL, respectively.
The purpose of the invention is realized by the following technical scheme:
(1) screening of active peptides
The invention carries out virtual enzyme digestion on a collagen sequence by means of an online enzyme digestion tool ExPASY Peptidecutter (http:// web. expask. org/peptide _ cutter /), and totally releases 111 peptide sequences. The biological activity, water solubility and toxicity of the obtained peptide sequence are predicted by ADMET modules of an online program PeptideRanker, peptide property calculator and Discovery Studio (DS), and 25 bioactive peptides with good biological activity, water solubility and no toxicity are obtained by screening. The 3D structure of tyrosinase (PDB ID: 2Y9X) was obtained from Protein Data Bank (PDB) database and used as receptor Protein, and DS software was used to perform molecular docking screening of peptides capable of binding tightly to tyrosinase active site. The 'CDOCKER _ Energy' value is taken as a screening index to obtain three peptides SDW, GAR and DGL which have the most potential tyrosinase inhibitory activity.
(2) In vitro tyrosinase inhibitory Activity assay
The inhibitory activity of the peptides SDW, GAR, and DGL on tyrosinase was determined spectrophotometrically. Taking peptide solutions with different concentrations, adding tyrosinase, incubating at 25 ℃ for 5min, adding L-dopa solution, reacting for 5min, and immediately determining the absorbance value of the reaction solution at 475nm after the reaction is finished.
The tyrosinase inhibition rates were calculated for different concentrations of peptide using the following formula:
tyrosinase inhibitory activity (%) [ (A-B) - (C-D) ]. times.100/(A-B)
Wherein A is an absorbance value of a reaction solution containing no inhibitor, B is an absorbance value of a reaction solution containing no inhibitor and an enzyme reaction solution, C is an absorbance value of a reaction solution containing L-dopa, and D is an absorbance value of a reaction solution containing no enzyme reaction solution. IC (integrated circuit)50Defined as the concentration of inhibitor that inhibits 50% of tyrosinase activity under the assay conditions.
Compared with the prior art, the invention has the following beneficial effects:
the invention screens and obtains the peptides SDW, GAR and DGL which can effectively inhibit the activity of tyrosinase from collagen, and defines the molecular action mechanism of active peptide and the active site of tyrosinase. The active peptides SDW, GAR and DGL can effectively inhibit the activity of tyrosinase and the generation of melanin, so that the active peptides SDW, GAR and DGL can be used as whitening functional components for cosmetics and health care products, and have good application prospects.
Drawings
The invention is illustrated in figure 1, wherein:
FIG. 1 shows the molecular docking results 2D of DGL with tyrosinase;
Detailed Description
The invention will now be further illustrated by means of specific examples
Example 1 screening of active peptides having tyrosinase inhibitory Activity
The invention selects pepsin (EC 3.4.23.1) and trypsin (EC 3.4.21.4) in an online enzyme digestion website ExPASY peptide cutter (http:// web. ExPASy. org/peptide _ cutter /) to carry out virtual enzymolysis on collagen, thereby obtaining 111 peptide sequences. The ADMET modules of an online tool PeptideRanker, peptide property calculator and Discovery Studio are used for respectively predicting the biological activity, water solubility and toxicity of the obtained peptide sequences, and 25 bioactive peptides with the biological activity scores higher than 0.5, good water solubility and no toxicity are obtained by screening, and are shown in Table 1.
Table 1 bioactivity, water solubility, toxicity prediction and molecular docking results for peptides
The crystal structure of tyrosinase (PDB ID: 2Y9X) was obtained from the PDB database, with the removal of water molecules, hydrogen atoms and definition of the acceptor protein, with the active neutral coordinate x: -10.044, y: -28.706, z: -43.443. The active peptide 3D structure was mapped with DS software, energy minimized using minize Ligands module, and as small molecule ligand. Molecular docking was performed by the CDOCKER program in DS to evaluate how tightly the active peptide binds to tyrosinase. Three polypeptides SDW, GAR and DGL with the most potential tyrosinase inhibitory activity are obtained by screening according to the docking score '-CDOCKER _ Energy' value and are shown in Table 1. The results indicate that all three active peptides bind to the tyrosinase residues His85, His244, His259, and Asn260, and that hydrogen bonding and van der waals interactions are the primary forces for peptide binding to tyrosinase.
Example 2 identification of tyrosinase inhibitory Activity in vitro of the peptides SDW, GAR and DGL
The inhibitory activity of tyrosinase on the active peptides SDW, GAR and DGL was determined by spectrophotometry. 60 μ L of peptide solutions of different concentrations were added to 40 μ L (500U/mL) of tyrosinase solution and incubated at 25 ℃ for 5 min. The reaction was then started by adding 200. mu. L L-dopa solution (0.5mM), and the absorbance at 475nm of the reaction solution was measured immediately after completion of the reaction at 25 ℃ for 5 min.
The tyrosinase inhibition rates were calculated for different concentrations of peptide using the following formula:
tyrosinase inhibitory activity (%) [ (A-B) - (C-D) ]. times.100/(A-B)
Wherein A is an absorbance value of a reaction solution containing no inhibitor, B is an absorbance value of a reaction solution containing no inhibitor and an enzyme reaction solution, C is an absorbance value of a reaction solution containing L-dopa, and D is an absorbance value of a reaction solution containing no enzyme reaction solution. IC (integrated circuit)50Defined as 50% inhibition under assay conditionsInhibitor concentration of tyrosinase activity.
Tyrosinase activity definition: the amount of enzyme required to catalyze the production of 1moL of dopaquinone from L-dopa at 25 ℃ is defined as one unit (U) of tyrosinase activity.
The results indicate that the peptides SDW, GAR and DGL are all effective in inhibiting tyrosinase activity, its IC50The values were 0.84mg/mL, 0.34mg/mL, and 0.15mg/mL, respectively.
Example 3 use of the tyrosinase inhibiting peptides SDW, GAR, DGL
In the actual production, the tyrosinase inhibitory peptides SDW, GAR and DGL can be obtained by solid phase synthesis or directed biological enzymolysis and purification, and are prepared into granular, powder or liquid dissolved in water to be added into health products, which is helpful for improving chloasma on human faces. The active peptide can also be added into conventional facial cleanser, facial mask and cream to prepare whitening cosmetics.
The technical solutions of the present invention are described in detail in the embodiments described above, it should be understood that the above are only specific embodiments of the present invention, and are not intended to limit the present invention, and it should be noted that: it will be apparent to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention, and these changes and modifications should also be considered as within the scope of the invention.
Claims (1)
1. The amino acid sequence of the active peptide with the tyrosinase inhibition effect is Ser-Asp-Trp or Gly-Ala-Arg or Asp-Gly-Leu.
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Cited By (4)
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| CN115353548A (en) * | 2022-09-20 | 2022-11-18 | 华南农业大学 | Pearl oyster tyrosinase inhibitory peptide with whitening effect and application thereof |
| CN115477686A (en) * | 2022-09-22 | 2022-12-16 | 北海黑珍珠海洋生物科技有限公司 | Pearl oyster active peptide with whitening effect and application thereof |
| CN117106016A (en) * | 2023-09-01 | 2023-11-24 | 海南大学 | Donkey-hide gelatin source tyrosinase inhibitory peptide and application thereof |
| CN117106015A (en) * | 2023-09-01 | 2023-11-24 | 海南大学 | Coconut-derived active peptide and application thereof |
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| CN108379550A (en) * | 2018-05-31 | 2018-08-10 | 吉林大学 | A kind of Corn source monomeric peptide is as the application in tyrosinase inhibitor |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115353548A (en) * | 2022-09-20 | 2022-11-18 | 华南农业大学 | Pearl oyster tyrosinase inhibitory peptide with whitening effect and application thereof |
| CN115353548B (en) * | 2022-09-20 | 2024-03-15 | 华南农业大学 | Pearl shell tyrosinase inhibitory peptide with whitening effect and application thereof |
| CN115477686A (en) * | 2022-09-22 | 2022-12-16 | 北海黑珍珠海洋生物科技有限公司 | Pearl oyster active peptide with whitening effect and application thereof |
| CN115477686B (en) * | 2022-09-22 | 2024-01-30 | 北海黑珍珠海洋生物科技有限公司 | Pearl shell active peptide with whitening effect and application thereof |
| CN117106016A (en) * | 2023-09-01 | 2023-11-24 | 海南大学 | Donkey-hide gelatin source tyrosinase inhibitory peptide and application thereof |
| CN117106015A (en) * | 2023-09-01 | 2023-11-24 | 海南大学 | Coconut-derived active peptide and application thereof |
| CN117106015B (en) * | 2023-09-01 | 2024-04-26 | 海南大学 | Coconut-derived active peptide and application thereof |
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