A dry-cured ham-derived DPP-IV inhibitory peptide and its preparation, identification method and application

Abstract

The invention discloses a dry-cured ham-derived DPP-IV inhibitory peptide and its preparation, identification method and application, and belongs to the technical field of DPP-IV inhibitory peptides. The identification method of the DPP-IV inhibitory peptide provided by the invention can quickly obtain the DPP-IV inhibitory peptide with the best inhibitory activity, realize high-throughput detection of polypeptides, and is time-saving, efficient, low-cost, accurate, more comprehensive, and practical, and can be used for the identification of DPP-IV inhibitory peptides; the dry-cured ham-derived DPP-IV inhibitory peptide obtained by the identification method provided by the invention has the advantages of hydrophobicity, easy absorption by the small intestine, fast metabolism, non-toxicity, good matching with the target protein, and can form a stable complex, and has good application prospects for lowering blood sugar.

Description

Technical Field

[0001] The present invention relates to the technical field of DPP-IV inhibitory peptides, in particular to a dry-cured ham-derived DPP-IV inhibitory peptide and a preparation method, an identification method and an application thereof. Background Art

[0002] Diabetes is a metabolic disease characterized by high blood sugar due to defective insulin secretion or impaired insulin action. According to the IDF Diabetes Atlas (2021), 10.5% of the adult population (20-79 years old) suffer from diabetes. According to IDF forecasts, by 2045, 1 in 8 adults (about 783 million people) will suffer from diabetes, an increase of 46%. The hazards of diabetes include a series of complications caused by it: blindness, heart disease, kidney failure, skin ulcers, foot numbness and dementia. At present, the main treatment preparations for diabetes include: metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sulfonylureas, glinide, α-glucosidase inhibitors, and glucagon-like peptide-1 receptor agonists-GLP1RA.

[0003] Currently, one of the main therapeutic targets for type 2 diabetes is dipeptidyl peptidase-IV (DPP-IV), which can decompose the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 can enhance glucose-induced insulin secretion and inhibit glucagon secretion to regulate the body's blood sugar level. Currently, the common DPP-IV inhibitory drugs on the market include sitagliptin, saxagliptin, vildagliptin, linagliptin and alogliptin, but the above inhibitors have many adverse reactions, such as gastrointestinal adverse symptoms, respiratory tract infections, skin diseases, etc.

[0004] Therefore, the development of DPP-4 inhibitors derived from natural foods with no or minimal side effects has attracted widespread attention. Studies have discovered multiple DPP-IV inhibitory peptides from plants such as rapeseed, peas, chickpeas, and broccoli. In addition, aquatic animals and eggs also have peptides with DPP-IV inhibitory potential. However, these food-borne DPP-IV inhibitory peptides need to be produced by protease hydrolysis.

[0005] The peptides in dry-cured ham are different from those extracted from other natural foods. During the fermentation and maturation of dry-cured ham, the proteins contained in it will be degraded into natural small peptides and amino acids under the action of endogenous enzymes. Therefore, obtaining active peptides in dry-cured ham only requires a simple extraction process.

[0006] At present, the preparation and identification method of active peptides is to gradually purify the activated peptides through laboratory experiments, which is labor-intensive, time-consuming, and costly, and it is difficult to apply in a high-throughput manner. Therefore, it is of great practical significance to develop a rapid and efficient method for identifying DPP-IV inhibitory peptides. Summary of the invention

[0007] The purpose of the present invention is to provide a dry-cured ham-derived DPP-IV inhibitory peptide and a preparation, identification method and application thereof, so as to solve the defects of the current identification method of DPP-IV inhibitory peptide being labor-intensive, time-consuming and costly, and to provide a dry-cured ham-derived DPP-IV inhibitory peptide.

[0008] To achieve the above object, the present invention provides a method for identifying a DPP-IV inhibitory peptide, the specific steps of which are as follows:

[0009] S1. Search and / or screen the obtained peptides using the Web of Science database;

[0010] S2, predicting the activity of the peptides screened in step S1;

[0011] S3, predicting the hydrophobicity of the peptides screened in step S2;

[0012] S4, predicting the cell penetration of the peptides screened in step S3;

[0013] S5, predicting the toxicity of the peptides screened in step S4;

[0014] S6, predicting the absorption performance and metabolic performance of the peptide segments screened out in step S5;

[0015] S7, using BIOPEP database Katedra Biochemii (uwm.edu.pl) Perform comprehensive simulation scores on the peptides obtained in step S6, and select the peptides with the highest comprehensive simulation scores as DPP-IV inhibitory peptides;

[0016] S8. Performing molecular docking simulation on the DPP-IV inhibitory peptide obtained in step S7 to screen and obtain the DPP-IV inhibitory peptide with the best activity.

[0017] Preferably, the search and / or screening conditions in step S1 are: peptides whose second amino acid at the N-terminus is Pro or Ala and whose length is 3-8 amino acids; the tool for predicting the activity of peptides in step S2 is Peptide Ranker or other tools with peptide activity prediction function, and active peptides with a Peptide Ranker score>0.5 are selected.

[0018] Preferably, the tool for predicting the hydrophobicity of peptides in step S3 is https: / / www.novopro.cn / tools / calc_peptide_property.html or other tools with peptide hydrophobicity prediction function, and peptides with high hydrophobicity are selected; the tool for predicting the cell penetrability of peptides in step S4 is CPPpred or other tools with peptide cell penetrability prediction function, and peptides with good cell penetrability are selected.

[0019] Preferably, the tool for predicting the toxicity of peptides in step S5 is https: / / webs.iiitd.edu.in / raghava / toxinpred or other tools with peptide toxicity prediction function, and non-toxic peptides are selected.

[0020] Preferably, the tool used to predict the absorption performance and metabolic performance of the peptide segment in step S6 is an ADMET prediction tool, the website of the ADMET prediction tool is http: / / lmmd.ecust.edu.cn / admetsar2, and human small intestinal digestion, CPY450 and acute oral toxicity are used as prediction indicators to select peptides with good absorption performance and metabolic performance.

[0021] An application of the identification method as described above in the identification of DPP-IV inhibitory peptides.

[0022] The dry-cured ham DPP-IV inhibitory peptide obtained by the above identification method is Leu-Pro-Pro-Asp-Tyr; Tyr-Ala-Asp-Phe-Lys; Leu-Pro-Val-His-Phe-Tyr; Arg-Pro-Pro-Trp-Val-Thr; Ala-Pro-Pro-His-Leu-Phe; Tyr-Pro-Leu-Ala-Lys-Gly.

[0023] A use of the dry-cured ham DPP-IV inhibitory peptide as described above in the treatment of type 2 diabetes.

[0024] A method for preparing the dry-cured ham DPP-IV inhibitory peptide as described above comprises the following steps:

[0025] (1) removing muscle fat and fascia tissue from the Anhui style dry-cured ham, mincing the remaining part, adding hydrochloric acid, homogenizing under ice bath conditions, centrifuging to obtain the supernatant, separating by membrane separation technology, and drying the retentate with a molecular weight of <3 kDa to obtain a crude peptide powder;

[0026] (2) The crude peptide powder was redissolved to prepare a crude peptide solution, and then filtered with an aqueous microporous filter membrane, separated and purified with a macroporous resin column, and separated and purified with a dextran gel exclusion chromatography to obtain three components, HPF-1, HPF-2, and HPF-3;

[0027] (3) HPF-2 is selected for high-resolution mass spectrometry identification of the amino acid composition of the polypeptide, and then the identification method described in any one of claims 1 to 7 is used for identification to obtain the DPP-IV inhibitory peptide of Hui style dry-cured ham.

[0028] Preferably, the drying in step (1) is freeze-drying; the pore size of the aqueous phase microporous filter membrane in step (2) is 0.45 μm, and the conditions for separation and purification by large-pore resin chromatography column are: the sample volume is 20 mL, the elution flow rate is 5-10 mL / min, and the components are first eluted with ultrapure water, and then eluted with 50% ethanol when the baseline is stable; the conditions for separation and purification by dextran gel exclusion chromatography are: before separation and purification, the components are redissolved in ultrapure water, and then applied to Sephadex G-30 pre-loaded column for separation and purification, the flow rate is 24 mL / h, the sample volume is 2 mL, and the absorbance is measured at a wavelength of 214 nm.

[0029] Therefore, the present invention provides a dry-cured ham-derived DPP-IV inhibitory peptide and its preparation, identification method and application, and its specific technical effects are as follows:

[0030] (1) The method for identifying DPP-IV inhibitory peptides provided by the present invention can quickly obtain DPP-IV inhibitory peptides with the best inhibitory activity by combining an effective database with molecular docking simulation of the main action targets of DPP-IV inhibitory peptides, thereby realizing rapid and high-throughput detection of polypeptides, with short time consumption, high efficiency, low cost, good accuracy, more comprehensive detection, and good practicality, and can be used for the identification of DPP-IV inhibitory peptides;

[0031] (2) The DPP-IV inhibitory peptide derived from the Anhui style dry-cured ham obtained by the identification method provided by the present invention has a high DPP-IV inhibitory activity, and at the same time has the advantages of being hydrophobic, easily absorbed by the small intestine, fast metabolic rate, non-toxic, and having good matching with the target protein, and can form a stable complex, and has good application prospects in lowering blood sugar.

[0032] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative labor.

[0034] Figure 1 The peptide concentration of each component of the crude peptide of Huizhou dry-cured ham and the IC of DPP-IV in Example 1 are 50 value;

[0035] Figure 2 The absorption peak (A), the absorption peak of the gel filtration component (B), the peptide concentration of the gel purification peak and the DPP-IV inhibitory activity (C) of the crude peptide powder of Hui-style dry-cured ham <3 kDa purified by DA201-C resin desalting in Example 1;

[0036] Figure 3 is the Nano-HPLC-MS / MS analysis and partial mass spectrum of HPF-2 in Example 1, wherein A is a schematic diagram of the total ion source and the number of peptides with different molecular weight cutoffs identified from HPF-2, and B is the MS / MS spectrum of the screened peptides;

[0037] Figure 4 The molecular docking results of the polypeptides RPPWVT (A), APPHLF (B), LPPDY (C), LPVHFY (D), YADFK (E) and YPLAKG (F) in Example 2 with DPP-IV;

[0038] Figure 5 is the molecular dynamics simulation result in Example 2, wherein A is the root mean square deviation of the screened peptide, B is the gyration radius and C is the number of hydrogen bonds;

[0039] Figure 6 It is the Lineweaver-Burk bilinear graph of the DPP-IV inhibitory peptides LPPDY (A), APPHLF (B), RPPWVT (C), LPVHFY (D), YADFK (E), and YPLAKG (F) in Example 3. DETAILED DESCRIPTION

[0040] The technical solution of the present invention is further described below through the accompanying drawings and embodiments.

[0041] In order to make the purpose, technical scheme and advantages of the present application clearer, more thorough and more complete, the technical scheme of the present invention is clearly and completely described below through the accompanying drawings and examples. The following detailed descriptions are all descriptions of the embodiments, and are intended to provide further detailed descriptions of the present invention. Unless otherwise specified, all technical terms used in the present invention have the same meaning as those generally understood by those skilled in the art to which the present application belongs.

[0042] The experimental methods in the following examples are all conventional methods unless otherwise specified. The experimental materials used in the following examples are all purchased from conventional biochemical reagent stores unless otherwise specified.

[0043] Embodiment 1

[0044] The peptides with different molecular weights were prepared using Anhui style dry-cured ham as raw material, and the steps are as follows:

[0045] 1. Prepare crude peptide. The specific steps are as follows:

[0046] The muscle fat and fascia tissue of the Hui-style dry-cured ham minced meat were removed, and then 20 g was weighed, added to 100 mL 0.01 M HCl, homogenized in an ice bath, homogenized at 16000 g for 6 times, each time for 30 s, and then centrifuged at 12000 g and 4 ° C for 20 min. The supernatant in the centrifuge tube was separated by membrane separation technology, and the components with molecular weights >3 kDa, <3 kDa, 1-3 kDa, and <1 kDa were retained respectively. The retained components were freeze-dried for 24 h to obtain the Hui-style dry-cured ham crude peptide powder, which was stored at -20 ° C for later use.

[0047] The OPA method was used to determine the polypeptide content, containing 25 mL of 100 mM borax, 2.5 mL of 20% (w / w) sodium dodecyl sulfate, 40 mg of o-phthalaldehyde dissolved in 1 mL of methanol, 100 μL of β-mercaptoethanol, and dilute to 50 mL with deionized water. Different concentrations of glutathione were used to make a standard curve. 50 μL of sample solution reacted with 2 mL of reagent at room temperature for 2 minutes, and colorimetric analysis was performed at 340 nm. The polypeptide content was obtained by comparing the standard curve. The polypeptide content in each component is shown in the following table. Figure 1 The contents of polypeptides >3kDa, <3kDa, 1-3kDa, and <1kDa were 42.53%, 53.45%, 37.83%, and 47.63%, respectively.

[0048] N-glycylprolyl-p-nitroaniline hydrochloride was used as a substrate and the absorption peak was detected at 405 nm. The in vitro DPP-IV inhibitory activity of each component was determined according to the method of Zhao Mouming et al. Figure 1 As shown, the fraction <3 kDa had the best inhibitory activity, so the fraction <3 kDa was selected for subsequent experiments.

[0049] 2. Purify the polypeptide obtained in step 1. The specific steps are as follows:

[0050] a Desalting: Weigh 5g of the <3kDa Anhui style dry-cured ham crude peptide powder prepared in step 1, add it to 10mL of pure water, re-dissolve it into a 500mg / mL crude peptide solution, filter it with a 0.45μm aqueous microporous filter membrane, load 5mL, elute at a flow rate of 1.5mL / min, first elute with ultrapure water, and then elute with 50% ethanol when the baseline is stable, and detect the absorption peak at a wavelength of 214nm. The results are as follows Figure 2 As shown in A.

[0051] b Gel purification: 50 mg of the Anhui style dry-cured ham polypeptide powder obtained after desalting was dissolved in 2 mL of 0.01 M HCl, and then passed through a 0.45 μL filter and eluted at a rate of 24 mL / h. The eluent was the same as the solvent, and the sample volume was 2 mL.

[0052] The protein purification system was used to detect the absorption peak at a wavelength of 214 nm and the samples corresponding to each peak were collected. Figure 2 As shown in B, a total of three components were obtained, named HPF-1, HPF-2 and HPF-3. The three components were collected and the polypeptide concentrations of the three components were detected using the method of step 1. The results are as follows Figure 2 As shown in C, the concentration of HPF-2 peptide is higher than that of HPF-1 and HPF-3. The inhibitory ability of the three components on DPP-IV is detected by the same method as step 1. The results are as follows Figure 2 As shown in C, HPF-2 has the strongest inhibitory ability on DPP-IV.

[0053] cHigh resolution mass spectrometry analysis:

[0054] HPF-2 was analyzed by LC-MS / MS equipped with an online nanospray ion source. The entire system was an Orbitrap Q-Exactive Plus mass spectrometer (Thermo Fisher Scientific, MA, USA) connected in series with an EASY-nanoLC1200. A total of 5 μL of sample was loaded (analytical column: Acclaim PepMap C18, 75 μm x 25 cm), and the sample was separated by a gradient of 60 min. The column flow was controlled at 300 nL / min, the column temperature was 40 °C, the electrospray voltage was 2 kV, and the gradient started from 2% of phase B, increased to 35% in 47 min with a nonlinear gradient, increased to 100% in 1 min, and maintained for 12 min.

[0055] The mass spectrometer was operated in data-dependent acquisition mode, automatically switching between MS and MS / MS acquisition. The mass spectrometry parameters were set as follows: (1) MS: scan range (m / z): 200-2000; resolution: 70,000; AGC target: 3e 6 ; Maximum injection time: 50ms; (2) HCD-MS / MS: resolution: 17,500; AGC target: 1e 5 ; Maximum injection time: 45ms; Collision energy: 28%, 35%, 48%; Dynamic exclusion time: 30s.

[0056] The results are as follows Figure 3 As shown, the mass spectrometry data were sorted and peptides with an abundance of 0 and no database protein source were removed.

[0057] The tandem mass spectra were analyzed by PEAKS Studio version 10.6 (Bioinformatics Solutions Inc., Waterloo, Canada). PEAKSDB searched the uniprot-Sus_scrofa (version 2023, 22841 entries) database and set None digestion. The search parameters were fragment ion mass tolerance: 0.02 Da, parent ion mass tolerance: 10 ppm, variable modification: Oxidation (M) 15.99, Deamination (NQ) 0.98, protein card value was at least 1 unique peptide; peptide card value was -101 gP ≥ 20. The results are as follows Figure 3 As shown in A, a total of 1075 peptides were screened, most of which had a molecular mass of 300Da-800 Da, accounting for 57.6%, further illustrating that short peptides have a higher relative inhibitory activity against DPP-Ⅳ.

[0058] Embodiment 2

[0059] The steps of screening DPP-IV inhibitory peptides by combining computer methods are as follows:

[0060] (1) In silico analysis of identified peptide sequences using existing peptide databases

[0061] The Web of Science database was used to search and screen for short peptides of 3-8 amino acids with Pro / Ala as the second amino acid at the N-terminus.

[0062] (2) Use the peptide activity prediction tool Peptide Ranker to predict the active peptides screened in (1) and select active peptides with a score > 0.5.

[0063] (3) Use the hydrophobicity prediction tool https: / / www.novopro.cn / tools / calc_peptide_property.html to predict the hydrophobicity of the peptides obtained in (2) and select peptides with high hydrophobicity.

[0064] (4) The peptides obtained in (3) were screened using the cell permeability prediction tool CPPpred to select peptides with better cell permeability.

[0065] (5) The peptides obtained in (4) were screened using the toxicity prediction tool https: / / webs.iiitd.edu.in / ragha va / toxinpred to obtain non-toxic peptides.

[0066] (6) The ADMET prediction tool http: / / lmmd.ecust.edu.cn / admetsar2 was used to predict the absorption and metabolic properties of the peptides obtained in (5). Human small intestinal digestion, CPY450 and acute oral toxicity were used as prediction indicators to obtain peptides with good absorption and metabolic properties.

[0067] (7) Using the BIOPEP database Katedra Biochemii (uwm.edu.pl) The peptides obtained in (6) were comprehensively simulated and scored, and the top 10 peptides with the highest comprehensive simulation scores were selected as DPP-IV inhibitory peptides. The specific prediction score information of the 10 DPP-IV inhibitory peptides obtained is shown in Table 1.

[0068] Table 1

[0069]

[0070] As can be seen from Table 1, the activity prediction scores of the 10 peptides obtained are high, and hydrophobicity is generally present. The HIA value is positive, and the peptides screened by the phenotype can be absorbed in the small intestine. The CPY450 prediction results show that the metabolism rate of the peptides in the body is relatively fast. The toxicity results show that they are all grade III toxicity, which is relatively low.

[0071] (2) Molecular docking

[0072] The protein with ID 1wcy was downloaded from the RCSB database, and the peptide chain was modeled using Maestro 11.0 software. The peptide chain was designated as the ligand, and the DPP-IV protein was designated as the receptor. PyMOL (version 4.3.0) software (https: / / pymol.org / ) was used to separate the original ligand and protein structure, dehydrate and remove organic matter, and AutodockTools (http: / / mgltools.scripps.edu / downloads) was used to add hydrogen, check the charge, designate the atom type as AD4 type, calculate gasteiger, and build the docking grid box of the protein structure. The results are shown in Figure 4 shown.

[0073] After docking with Vina, the score of the 1wcy protein and peptide chain docking combination was calculated, and Pymol and Discovery Studio software were used for three-dimensional and two-dimensional force analysis and visualization. Docking energy is generally negative, and the smaller the value, the higher the score of the docking result, that is, the tighter the binding between the ligand and the receptor protein, the stronger the interaction, and the more likely it is to have DPP-IV inhibitory activity.

[0074] The molecular docking scores ranged from -6.9 kcal / mol (LPVKYL) to -9.8 kcal / mol (LPVHFY). In other studies, the absolute value of the molecular docking Vina score was positively correlated with the inhibitory activity, so 6 peptides with scores ≤ -7.8 kcal / mol were selected. The scores of LPPDY, LPVHFY, YPLAKG, RPPWVT, and APPHLF were -7.8 kcal / mol, respectively. All of them were able to bind tightly to the target protein. It binds to the active site of DPP-IV (S1: Tyr547, Tyr631, Ser630, Tyr662, His740, Tyr666, Val656; S2: Glu206, Phe357, Tyr666, Tyr547, His740, Arg125 and Ser630) through hydrogen bonds and hydrophobic interactions. See Table 2.

[0075] Table 2

[0076]

[0077] (3) Molecular dynamics simulation

[0078] The Gromacs 2020 software package was used to perform molecular dynamics simulations on the screened receptor protein-peptide complexes. The protein used the AMBER99SB-ILDN force field parameters, the peptide ligand used the gaff2 general force field parameters, and the sobtop program was used to construct the peptide topology, and then RESP was used for charge fitting. The binding free energy of the ligand and protein was calculated using the g_MMPBSA method of the Gromacs 2020 program. The results are shown in Figure 5 shown.

[0079] RMSD is the sum of the deviations of all atomic positions between the calculated conformation at a certain moment and the initial conformation. Monitoring the RMSD of a protein can provide a deep understanding of the structural conformation of the complex and measure stability during the entire simulation process. The wider the distribution range of RMSD values, the richer the changes in the molecular conformation. The results are as follows: Figure 5 As shown in A, the complexes of the six peptides and the target protein basically reached a dynamic equilibrium in about 5ns, indicating that the six peptides matched the target protein well and could form a stable complex.

[0080] In order to analyze the relative compactness and stability of the complex induced by binding at the primary and secondary sites, the radius of gyration (Rg) of the target protein was measured, that is, the mass-weighted position distance between the receptor atoms and the center of mass was calculated. The Rg diagram is shown in Figure 5 As shown in B, it can be seen that the Rg of the six complex proteins decreased to a certain extent during the simulation. This may be because after molecular dynamics, the binding of the protein and the polypeptide prompted the protein to maintain more hydrophobic contacts and form more effective interactions inside the protein to better match the polypeptide, thereby promoting the stability of the complex.

[0081] In order to gain a more intuitive understanding of the binding between proteins and peptides, the changes in the number of hydrogen bonds between proteins and peptides during the entire simulation process were statistically analyzed. The results are as follows: Figure 5 As shown in Figure 3C, the peptides are able to form three or more hydrogen bond interactions with the protein pocket amino acids. These hydrogen bonds play an important role in stabilizing the binding of peptides and proteins.

[0082] Embodiment 3

[0083] Six short peptides were synthesized by solid phase method according to the polypeptide sequence obtained in Example 2, and the six short peptides were tested for in vitro DPP-IV inhibitory activity in the same manner as in Example 1. The results are shown in Table 2. It can be seen that LPPDY and LPVHFY have strong DPP-IV inhibitory abilities, with a maximum half inhibitory concentration (IC 50 ) reached 197.38μM and 41.44μM respectively.

[0084] Peptide-based IC 50The Lineweaver-Burk double reciprocal curve was prepared with different concentrations of Gly-Pro-pNA (0.2-1mM). Figure 6 As shown, peptides with strong DPP-IV inhibitory activity have a competitive inhibition mode.

[0085] Lineweaver-Bur formula:

[0086]

[0087] In summary, the DPP-IV inhibitory activity of the Anhui style dry-cured ham source identified in the present invention is relatively high. It is mainly bound to the active site of the target protein through hydrogen bonds and hydrophobic interactions, and occupies the binding site of the DPP-IV protein and GLP-1, thereby inhibiting the activity of DPP-IV, thereby reducing blood sugar levels, and has a very high DPP-IV inhibitory activity.

[0088] Therefore, the identification method of the DPP-IV inhibitory peptide provided by the present invention can quickly obtain the DPP-IV inhibitory peptide with the best inhibitory activity, realize high-throughput detection of the polypeptide, and has short time consumption, high efficiency, low cost, good accuracy, more comprehensive detection, good practicality, and can be used for the identification of the DPP-IV inhibitory peptide; the Hui style dry-cured ham source DPP-IV inhibitory peptide obtained by the identification method provided by the present invention has the advantages of hydrophobicity, easy absorption by the small intestine, fast metabolism, non-toxicity, good matching with the target protein, and can form a stable complex, and has good application prospects for lowering blood sugar.

[0089] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A dry-cured ham DPP-IV inhibitory peptide, characterized in that: The DPP-IV inhibitory peptide is Leu-Pro-Pro-Asp-Tyr; Tyr-Ala-Asp-Phe-Lys; Leu-Pro-Val-His-Phe-Tyr; Arg-Pro-Pro-Trp-Val-Thr or Tyr-Pro-Leu-Ala-Lys-Gly.

2. Use of the dry-cured ham DPP-IV inhibitory peptide as claimed in claim 1 in the preparation of a drug for the treatment of type 2 diabetes.

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