CN113321710B - Polypeptide with function of promoting enamel structural mineralization and regeneration - Google Patents
Polypeptide with function of promoting enamel structural mineralization and regeneration Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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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 polypeptide with the function of promoting the structural mineralization and regeneration of enamel. The invention provides a polypeptide, the sequence of which is as follows: NH2GHPGYINFSYEVLTQPYQPVQPHQPMQPQTKREEVD-COOH, the invention also provides nucleic acid molecules encoding said polypeptides. The polypeptide of the invention has the following advantages: the amino acid is composed of 36 amino acids, is relatively short, can be prepared by chemical synthesis and is convenient to be prepared by recombinant expression; the polypeptide sequence is different from the existing peptide chain with the function of inducing enamel mineralization; the polypeptide sequence provided by the invention has an induction effect on the structural mineralization of enamel with acid etching defects.
Description
Technical Field
The invention relates to a polypeptide with the function of promoting the structural mineralization and regeneration of enamel.
Background
As one of the hardest substances in the human body, enamel covering the crown is an important component for protecting teeth against daily wear and chemical erosion. Among the components of mature enamel, hydroxyapatite [ HAP, Ca ]10(PO4)6(OH)2]Accounts for the most part, up to 96% by weight (Mann A, Dickinson M. Nanomechanics, chemistry and structure at the architectural surface. in: Duckworth RM, edition. the tea and the environment. monograms in organic Science 2006; 19:105-31.), while organic and water account for 1% and 3%, respectively. Unlike conventional hydroxyapatite crystals, enamel has such excellent corrosion resistance and abrasion resistance because the hydroxyapatite crystals contained therein exhibit a layered arrangement structure. The composition of enamel is based on hydroxyapatite crystals 50nm wide, 25nm thick and several microns long. The crystals induced and mineralized by the same ameloblast are mutually arranged and gathered to form a bundle of enamel pillars with the diameter of 3-5 mu m and the diameter similar to that of a single ameloblast (Janet moradial-Oldak. the REGENERATION of TOOTH ENAMEL. Dimenss Dent Hyg.2009; 7(8): 12-15.). After formation of the enamel pillars, the pillars and the inter-pillar enamel are woven with each other to finally form an enamel of about 2.5mm thickness. Normal ripe Enamel is slightly transparent in texture, not unique in color, and can range from yellow-white to off-white (Nanci, A. Ten Cat's Oral Histology Development, Structure, and function. St. louis: Mosby Elsevier; 2008. Environment: composition, formation, and Structure; p.141-190.).
The enameloblast plays an important role in the development process of enamel, and plays roles in secreting enamel matrix proteins (AMELX, ENAM, AMBN and the like), adjusting the pH value of the enamel matrix, transporting ions, absorbing protein fragments in the enamel matrix and the like. The protein AMELX is the major component of the Enamel matrix, accounting for approximately 90% (Lactruz RS, Habelitz S, Wright JT, pain ML. fractional engineering Format and improvements for Oral Health and disease. physical Rev 2017,97: 939-. Human AMELX (H175) has a peptide chain length of 175 (recombinant 174, also known as rH174), belongs to a bipolar molecule, in which most of the sequence is hydrophobic and contains hydrophilic amino acid residues at the carboxy-terminal (Xiaoodong He, Shenping Wu, Olga Martinez-Avila, Yifang, Stefan Habelite. self-aligning genes in nanoparticles in oil-water system. journal of Structural Biology 2011,174: 203-212.). It is believed that the bipolarity of AMELX is a prerequisite for AMELX to self-assemble into various nanostructures (Claussen, R.C., Rabatic, B.M., Stupp, S.I.,2003.Aqueous self-assembly of nonsystematic peptides from nanoparticles with hydrophic products and surfaces. J.am. chem. Soc.125, 12680-12681), which play an important role in the subsequent induction of HAP mineralization according to a certain structural rule. Before the enamel is mineralized to be mature, an enamel matrix with ordered structure is formed to induce HAP to be mineralized according to a certain direction, so that a specific crystal structure is formed. The mechanism of enamel matrix assembly in vitro can be divided into two stages (Xiudong Yang, Lijun Wang. how enamel in organisms the Organization of high architectural and electrically connected microstuctures of Apatite. J. Phys. chem. B2010, 114, 2293-: (1) controlled aggregation reactions and (2) the gradual hierarchical structure induction of crystal organized growth in specific directions as the AMELX-Ca-P nanoclusters develop.
Tooth enamel is infiltrated in the oral cavity by saliva secreted by the salivary glands. H contained in saliva+、Ca2+、HPO4 2-Plasma, so that hydroxyapatite crystals on the enamel surface are in a dynamic balance of mineralization and demineralization (Sollbohmer O, May KP, Anders M, Force microscopical introduction of human tissue in liquids Films 1995,264: 176-83.).
As can be seen from the above equation, if in a meta-acid environment (pH)<5.5) (Xiaoodong He, marketing Wu, Olga Martinez-Avila, Yifan Cheng, Stefan Habelitz. self-aligning amyloid in oils-water system. journal of Structural Biology 2011,174: 203-. If caries is deep and HAP crystals are damaged more, the damaged enamel cannot be repaired by mineralization and demineralization dynamic equilibrium reaction, and the original HAP crystal structure is recovered. In the process of tooth development, enamel forming cells playing an important role in enamel formation and a series of proteins related to enamel formation, mainly amelogenin, secreted by the enamel forming cells are gradually hydrolyzed and eliminated along with the mineralization and formation of enamel, and the enamel forming cells are also subjected to apoptosis after the formation of the enamel. Because of this, patients with serious caries can not repair damaged enamel through the body, and repair enamel through artificial means, so that the structural function of regenerated enamel is not obviously different from that of original enamel, which is the direction of efforts of researchers at present.
In the area of enamel regeneration, a common idea taken by researchers is biomimetic remineralization of enamel, i.e., the induction of crystal nucleation, orientation, and growth is achieved by constructing materials or substances through chemical and biological means. Wherein Yang Zhou et al designed a kind of elastin-like polypeptide. The polypeptide contains a plurality of carboxyl groups, and can promote more calcium ions in a solution to gather while being combined with ACP, thereby promoting mineralization (Yang Zhou, Yanling Zhou, Long Gao, Chengtie Wu a and Jiang Chang. Synthesis of aromatic dense peptide involved biological approach. J. Elastin-like polypeptide associated biological approach. chem. B,2018,6, 844.). AMELX, which plays an important role in the process of enamel development, has been the focus of research. LRAP is a variable cleavage product of a 56 amino acid residue long, AMELX. S.Y.KWak et al, using a method of LRAP in combination with inorganic pyrophosphate (PPi), induced formation of acicular HAP crystals by using LRAP and PPi to regulate the formation of mineralized tissue, Enamel crystals with similar structure were grown on the damaged Enamel surface (S.Y.KWak, A.Litman, H.C.Margolis, Y.Yamakoshi, and J.P.Simmer.biometric Ename Regeneration media by Leucine-Rich Amelogenin peptide.J Dent Res.2017,96(5): 524-530.). The crystals produced by this method, although well bonded to the cross-section of the damaged enamel, produced enamel with a certain number of voids. A highly conserved QPX sequence was present in AMELX, and was ligated to a hydrophilic fragment of AMELX, and was found to have a significant effect on the promotion of tooth mineralization in mice (Sili Han, Yingying Fan, Zhengli Zhou, Huangxin Tu, Danxue Li, Xueping Lv, Longjiang Ding, Linglin Zhang. the promotion of amino acids remineralization by amino acids, amino acids-derived peptides a. enzyme-derived enzymes, the origin of organic Biology 2017,73: 66-71.). Sii Han et al speculate that the peptide chains they synthesize are able to bind to mouse molar surfaces and self-assemble into a fibrous framework structure.
Disclosure of Invention
The embodiment of the invention aims to provide a polypeptide with the function of promoting the structural mineralization and regeneration of enamel.
The polypeptide with the function of promoting the structural mineralization and regeneration of enamel provided by the invention has the amino acid sequence as follows: NH (NH)2-GHPGYINFSYEVLTQPYQPVQPHQPMQPQTKREEVD-COOH。
According to a further technical scheme, the invention also protects the derivative of the polypeptide with the function of promoting the structural mineralization and regeneration of enamel, and the derivative is as follows (1) or (2):
(1) derivatives obtained by inserting and/or substituting and/or deleting one or more amino acid residues in the polypeptide;
(2) linking the polypeptide or the derivative of (1) with a carrier to obtain the derivative.
In a further technical scheme, the application of the polypeptide or the derivative in preparing the medicament for treating enamel remineralization also belongs to the protection scope of the invention.
According to a further technical scheme, the invention also protects an enamel remineralization mode, wherein the mode is that the polypeptide is mixed with a calcium-phosphorus ion solution containing pyrophosphate for use, so that enamel is remineralized.
In a further technical scheme, the invention also protects an enamel remineralization liquid, and the active ingredient of the enamel remineralization liquid is the polypeptide or the derivative of the polypeptide.
In a further technical scheme, the invention also protects a medicament for treating or preventing the tooth enamel surface defect, and the active ingredient of the medicament is the polypeptide or the derivative of the polypeptide.
The polypeptide with the function of promoting the structural mineralization and regeneration of enamel provided by the embodiment of the invention has the beneficial effects that:
(1) the preparation is convenient: the polypeptide consists of 36 amino acid residues, is relatively short, can be prepared by chemical synthesis or recombinant expression, and is easy to prepare;
(2) the polypeptide sequence differs from existing enamel remineralizing agents: the polypeptide provided by the invention has a definite effect, and can be mixed with a calcium-phosphorus ion solution containing pyrophosphate to promote remineralization of damaged enamel.
Drawings
FIG. 1 is a circular dichroism diagram of a polypeptide with the function of promoting enamel structural mineralization regeneration provided by the embodiment of the invention;
FIG. 2 is a transmission electron microscope image of a solution form of a polypeptide having the function of promoting the structural mineralization regeneration of enamel according to an embodiment of the present invention;
FIG. 3 is a scanning electron micrograph of acid etched enamel surface morphology;
FIG. 4 is a scanning electron microscope image of a control group with induced mineralization effect on acid-etched enamel surface by a polypeptide having the function of promoting enamel structural mineralization regeneration provided by an embodiment of the present invention;
FIG. 5 is a scanning electron microscope image of an experimental group A for acid-etched enamel surface induced mineralization effect, which is provided by the embodiment of the present invention, of a polypeptide having an enamel structural mineralization regeneration promoting function;
fig. 6 is a scanning electron microscope image of an experiment group B for inducing mineralization of an enamel surface by acid etching, which is provided by an embodiment of the present invention, with a polypeptide having an enamel structural mineralization regeneration promoting function;
fig. 7 is a scanning electron microscope image of an experiment group C for acid-etched enamel surface induced mineralization effect of a polypeptide having an enamel structural mineralization regeneration promoting function provided in an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified. In the quantitative experiments in the following examples, three replicates were set up and the results averaged.
Specific implementations of the present invention are described in detail below with reference to specific embodiments.
Example 1, there is a design of polypeptide for promoting the regeneration function of enamel structural mineralization, and the design principle is as follows:
before the enamel is mineralized to be mature, an enamel matrix with ordered structure is formed to induce hydroxyapatite to be mineralized according to a certain direction, so that a specific crystal structure is formed. The mechanism of assembly of the enamel matrix in vitro can be divided into two stages: (1) controlled aggregation reactions and (2) the gradual hierarchical structure induction of crystal organized growth in specific directions as the AMELX-Ca-P nanoclusters develop.
Human AMELX (H175) peptide chain length 175 (recombinant 174, also called rH174), belongs to bipolar molecules, most of which are hydrophobic and contain hydrophilic amino acid residues at the carboxyl terminal. It is considered that the bipolarity of AMELX is a precondition for the AMELX to self-assemble into various nanostructures, and the nanostructures play an important role in the subsequent induction of the mineralization of HAP according to a certain structural rule.
In view of the bipolar and self-assembly properties of AMELX above, a polypeptide is designed based on the amino acid sequence of the 8-21 segment of AMELX with a very high tendency to self-assembly and the highly conserved QPX sequence, the polypeptide is 36 amino acids in length, wherein the carboxyl end has a hydrophilic segment of 7 amino acids in length. The polypeptide has good induced mineralization effect on acid-etched enamel samples after being mixed with calcium-phosphorus ion solution containing pyrophosphate.
The amino acid sequence of the polypeptide is as follows: NH (NH)2-GHPGYINFSYEVLTQPYQPVQPHQPMQPQTKREEVD-COOH. Hereinafter, the polypeptide in each embodiment refers to the sequence polypeptide.
Example 2 Synthesis of polypeptide, measurement of physicochemical Properties and morphological Observation
Synthesis of polypeptide
The polypeptides were chemically synthesized by Biotechnology engineering (Shanghai) GmbH. The polypeptide is lyophilized and stored at-20 ℃.
Second, the physicochemical Properties of the polypeptide (circular dichroism analysis)
1. Purpose of experiment
And determining the possible secondary structure of the polypeptide by measuring the absorbance of the polypeptide circular dichroism chromatogram.
2. Laboratory apparatus, reagent and method
The freeze-dried polypeptide powder is placed at 25 ℃ for 20 minutes to be unfrozen and then dissolved in double-distilled deionized water, the volume is determined to be 1mg/mL and the solution is used as a storage mother solution and is placed in a 37 ℃ constant temperature water bath box for 1 hour. The mean residue molar ovality coefficient of the polypeptides was determined using a Bio-Logic MOS-500 Circular Dichroism (CD) instrument at 25 ℃. Diluting 1mg/mL polypeptide solution by 100 times, adding the diluted solution into a 1cm quartz test tube, and scanning the solution from 180nm to 260nm to obtain the ellipticity coefficient of the product polypeptide. The CONTIN/LL algorithm was used to assess the proportion of each secondary structure of the polypeptide.
3. Results of the experiment
From the CD data in FIG. 1, the beta-sheet proportion of the polypeptide was 43.4% as calculated by CONTIN/LL algorithm. The proportion of beta-turn is 38.7 percent, and the proportion of irregular curling is 17.6 percent. The polypeptide is shown to be mainly in a beta-folded structure in double-distilled deionized water.
Thirdly, morphological observation of polypeptide (Transmission Electron microscope)
1. Purpose of experiment
And observing the molecular morphological structure of the polypeptide in the solution.
2. Laboratory apparatus, reagent and method
A calcium-phosphorus ion stock solution (133.6mM CaCl) prepared by dissolving it in double distilled water was added2，83.6mM KH2PO4) After 40-fold dilution, the polypeptide was dissolved so that the final concentration of the polypeptide in the solution was 0.8mg/mL, and the pH was adjusted to 4.5 using KOH. The solution was then incubated in a 37 ℃ water bath for 7 days. After 7 days, 2. mu.L of the solution was dropped on a carbon film copper net for 2 minutes and then blotted dry with filter paper, followed by negative staining with 1% phosphotungstic acid for 2 minutes and then washing with double distilled water, and the filter paper was wiped dry. The morphology of the polypeptide was observed with a JEOL JEM-1400 Transmission Electron Microscope (TEM) at 80 kV.
3. Results of the experiment
According to FIG. 2, the polypeptides are spheroid-like, with individual diameters of 10-23nm and an average diameter of 16 nm. The polypeptide is indicated to be a spheroid in calcium and phosphorus ion solution.
The polypeptides prepared in example 2 were used for the assays of the subsequent examples.
Example 3 remineralization of acid etched enamel by Polypeptides
First, preparation of acid etched enamel specimen
Bovine central incisors were cut into 5mm by 3mm (length by width by height) cuboids using an MTI SYJ-150 low speed diamond saw blade machine. Uniformly sanding with 180, 320, 600, 1200, 2500 mesh sandpaper in sequence, then rinsing with a large amount of double distilled water and ultrasonically cleaning with a Shumei KQ3200DB numerical control ultrasonic cleaner. A37% phosphoric acid etching agent was applied evenly on the cleaned and wiped dry enamel specimens for acid etching for 60 seconds followed by sufficient double distilled water rinsing. The acid etched enamel specimens were immersed in double distilled water and refrigerated at 4 ℃ for future use.
Secondly, preparation of enamel remineralization solution
A supersaturated calcium-phosphorus ion solution (1.5mM KH) was prepared by dissolving potassium dihydrogen phosphate, calcium chloride and sodium chloride in double distilled water and adding a small amount of sodium pyrophosphate2PO4,1.3mM CaCl2,50mM NaCl,0.01μM Na4P2O7). In the experimental group, the polypeptides were added in sequence according to different concentrationsAnd (3) putting the mixture into a supersaturated calcium-phosphorus ion solution (the polypeptide concentrations are 0.02, 0.04 and 0.06mg/mL in sequence, and the polypeptide concentrations are divided into an experimental group A, an experimental group B and an experimental group C in sequence). The control group was a supersaturated calcium phosphate solution without the addition of the polypeptide.
Third, enamel remineralization experiment
10 enamel specimens per group were added to the above control and each experimental group solution, followed by incubation in a 37 ℃ thermostated water bath for 48 hours. After incubation, the enamel slides were removed and rinsed with sufficient double distilled water for subsequent testing.
Fourth, the crystal form of enamel surface regeneration (scanning electron microscope)
1. Purpose of experiment
Observing the surface regeneration crystal morphology of the enamel sample, and evaluating the directional mineralization induction effect of the polypeptide.
2. Laboratory apparatus, reagent and method
Enamel specimens were removed from the control and experimental groups and oven dried at 50 ℃. Gold powder was sprayed on the enamel surface using an ion sputtering instrument to increase the conductivity of the sample. The surface of the enamel specimens was observed using a Hitach S-4800 Scanning Electron Microscope (SEM) in Japan at a voltage of 5 kV.
3. Results of the experiment
As a result, as shown in fig. 3, the enamel surface after acid etching by phosphoric acid showed pit concavity with pits uniformly distributed on the enamel surface, wherein the hydroxyapatite crystals were severely corroded to cause disappearance of the prism structure of the crystals. The highly ordered rod-like crystals become needle-like and cluster-like hydroxyapatite crystals. In addition, amorphous calcium covering with a higher electron density exists in a part of the region.
Results as shown in figure 4, in the control group without the addition of the polypeptide, the acid-etched pits on the enamel specimen surface were covered with a thicker layer of amorphous calcium. The amorphous calcium is uniform in texture, the surface layer of enamel is almost free from hydroxyapatite crystal formation, and the formed few crystals have the length of about 0.30-0.50 μm and the width of about 0.05 μm. Although a small amount of hydroxyapatite crystals are still formed, the growth directions of the formed crystal columns are different, the arrangement is disordered and staggered, and no typical hierarchical structure is formed.
As shown in fig. 5, 6 and 7, after the experimental groups are treated, the mineralized crystallization phenomenon is successfully generated on the acid-etched surface of the sample, so that the clustered needle-shaped hydroxyapatite is prolonged, and the formed crystal micro-column has a uniform width of about 0.07 μm on average. In the experimental group, only a small area was covered by the amorphous calcium layer, while the majority was the columnar layer grown in situ on the acid etched crystal. Although a hydroxyapatite crystal layer was grown in all experimental groups containing supersaturated calcium phosphorus solutions of the polypeptide, the concentration of the polypeptide affected the growth of the crystals in terms of length, width, orientation, alignment, etc.
With the increase of the polypeptide concentration in the experimental group, the arrangement form of the regenerated crystals is more ordered, and the direction of the microcolumns induced and mineralized by the acid-etched enamel crystal clusters is consistent with that of the original crystals. In addition, the newly formed microcolumns are parallel to each other and arranged closely without gaps.
Fifth, physical Properties of enamel specimens (microhardness test)
1. Purpose of experiment
The enhancement of physical properties of enamel specimens by said polypeptides is assessed by measuring the vickers hardness of the enamel specimens.
2. Laboratory apparatus, reagent and method
The acid etched enamel specimens as well as the test group a, test group B, and test group C enamel specimens were polished to a polished surface using 1200 mesh sandpaper. Hardness was measured using a microhardness tester, Shimadzu HMV-G20, Japan, with the pressure set at 100G for 15 seconds. Each enamel specimen was tested at 5 randomly selected sites and the results averaged.
3. Results of the experiment
The vickers hardness of the acid etched samples averaged 197.2HV0.1 due to demineralization of the enamel surface. After being soaked in calcium-phosphorus solution containing AIMP with different concentrations for remineralization, the hardness of the enamel surface is improved to different degrees. The vickers hardness of experimental group a increased to a mean of 241.6HV0.1 and the hardness of the enamel surface of experimental group B further increased to a mean of 246HV0.1, which is the best of the three experimental groups. While the enamel surface hardness of the experimental group C decreased to 218.6HV0.1, which is the lowest of the three experimental groups. All hardness measurements above show that the hardness of acid-etched enamel surfaces can be enhanced after treatment with a calcium phosphate solution containing AIMP. The results are shown in Table 1.
Table 1 acid etched enamel specimens and experimental group A, B, C average vickers hardness of enamel specimens
| Group of | Acid-etched | 0.02mg/mL AIMP | 0.04mg/mL AIMP | 0.06mg/mL AIMP |
| Vickers hardness (HV0.1) | 197.2 | 241.6 | 246 | 218.6 |
Sequence listing
<110> Jilin university
<120> polypeptide with function of promoting enamel structural mineralization regeneration
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 36
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 1
Gly His Pro Gly Tyr Ile Asn Phe Ser Tyr Glu Val Leu Thr Gln Pro
1 5 10 15
Tyr Gln Pro Val Gln Pro His Gln Pro Met Gln Pro Gln Thr Lys Arg
20 25 30
Glu Glu Val Asp
35
<210> 2
<211> 108
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 2
ggncayccng gntayathaa yttywsntay gargtnytna cncarccnta ycarccngtn 60
carccncayc arccnatgca rccncaracn aarmgngarg argtngay 108
Claims (4)
1. A polypeptide with the function of promoting the structural mineralization and regeneration of enamel is shown as a sequence 1, and the amino acid sequence is as follows: NH (NH)2-GHPGYINFSYEVLTQPYQPVQPHQPMQPQTKREEVD-COOH。
2. Use of a polypeptide having an enamel structural mineralization and regeneration promoting function according to claim 1 for preparing a medicament for treating enamel remineralization, wherein the polypeptide is mixed with a calcium-phosphorus ion solution containing pyrophosphate to promote the enamel remineralization treatment of damaged tooth surfaces mainly containing hydroxyapatite.
3. An enamel remineralization liquid, the active component of which is the polypeptide with the function of promoting the structural mineralization and regeneration of enamel according to claim 1; the polypeptide amino acid sequence is as follows: NH (NH)2-GHPGYINFSYEVLTQPYQPVQPHQPMQPQTKREEVD-COOH; the enamel structural mineralization regeneration is used for promoting the remineralization treatment of the tooth surface enamel defect of which the main component is hydroxyapatite by mixing the polypeptide with a calcium-phosphorus ion solution containing pyrophosphate.
4. A medicament for treating or preventing tooth enamel surface defects, wherein the active ingredient of the medicament is the polypeptide with the function of promoting the structural mineralization and regeneration of enamel according to claim 1; the polypeptide amino acid sequence is as follows: NH (NH)2-GHPGYINFSYEVLTQPYQPVQPHQPMQPQTKREEVD-COOH; the enamel structural mineralization regeneration is used for promoting the remineralization treatment of the tooth surface enamel defect of which the main component is hydroxyapatite by mixing the polypeptide with a calcium-phosphorus ion solution containing pyrophosphate.
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