A bifunctional active peptide with both ACE and DPP-IV inhibitory activity and its preparation method and application

Abstract

The invention discloses a bifunctional active peptide having both ACE and DPP‑IV inhibitory activity and its preparation method and application, and belongs to the field of active peptide biotechnology. The present invention prepares and identifies a bifunctional new active peptide having both ACE and DPP‑IV inhibitory activity from sea cucumber hydrolysate, not only can suppress the activity of ACE, but also has DPP‑IV inhibitory activity, and its bifunctionality makes it have the application value in preparing blood pressure lowering and hypoglycemic efficacy products. The active peptide involved in the present invention, can significantly suppress the activity of ACE, while possessing DPP‑IV inhibitory activity, with the characteristics of simple structure, safety, strong activity, the effect of nutrition and health care can be played, it is expected to provide effective active ingredients for developing food and hypotensive, hypoglycemic or hypotensive and hypoglycemic efficacy products without side effects, with a wide range of applications.

Description

Technical Field

[0001] The present invention relates to the field of active peptide biotechnology, and in particular to a bifunctional active peptide having both ACE and DPP-IV inhibitory activities, and a preparation method and application thereof. Background Art

[0002] Hypertension and type 2 diabetes are both serious diseases worldwide. Angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) play a key role in their pathogenesis. ACE catalyzes the conversion of angiotensin I to angiotensin II through the renin-angiotensin system (RAS), a key component of the blood pressure regulation system. It also regulates the kinase-kinase system (KKS), which degrades bradykinin, thereby contributing to elevated blood pressure. Therefore, inhibiting ACE activity is considered an important therapeutic approach for lowering blood pressure. DPP-IV is an enzyme widely expressed in the intestine and liver, involved in the degradation of numerous bioactive peptides. DPP-IV's primary substrates include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), both of which play crucial roles in blood glucose regulation. Inhibiting DPP-IV reduces the degradation of GLP-1 and GIP, increasing their concentrations and prolonging their effects, promoting insulin secretion and inhibiting glucagon secretion, thereby effectively lowering blood glucose levels. Therefore, inhibiting DPP-IV activity is considered an important therapeutic approach for lowering blood glucose. Although chemically synthesized ACE inhibitors (such as captopril and enalapril) and DPP-IV inhibitors (such as sitagliptin and vildagliptin) have demonstrated promising clinical efficacy in lowering blood pressure and blood sugar, their therapeutic properties can lead to potential side effects, limiting their long-term use. In contrast, functional peptides derived from natural proteins with ACE and DPP-IV inhibitory activity are a more ideal alternative due to their high safety profile and low side effects.

[0003] As a traditional marine organism rich in various nutrients, sea cucumbers are high in protein and low in fat. They have multiple functions, including enhancing immunity, promoting growth and development, and regulating blood lipids. Their main nutrients include collagen, sulfated polysaccharides, sea cucumber saponins, and a wealth of trace elements, vitamins, and minerals. In particular, sea cucumbers are rich in up to 50% protein, making them a high-quality protein source. Protein is a crucial component for tissue repair and regeneration, and is crucial for maintaining life. The abundant protein resources in sea cucumbers offer great potential for generating functional products after hydrolysis. Furthermore, sea cucumbers have long been considered a valuable traditional tonic food and are considered safe and reliable. Processing byproducts such as sea cucumber intestines and eggs have also been shown to contain significant amounts of protein, making them important raw materials for the development of functional products. Exploiting these raw materials to generate functional products not only facilitates the development of active ingredients but also significantly increases the value-added utilization of sea cucumber byproducts. Existing studies have shown that enzymatic hydrolysis products obtained from sea cucumbers exhibit certain ACE and DPP-IV inhibitory activities, potentially allowing the discovery of multifunctional peptides that inhibit both ACE and DPP-IV. This not only helps develop high-value-added functional foods, but also provides new auxiliary treatments for natural interventions in hypertension and type 2 diabetes. Summary of the Invention

[0004] The purpose of the present invention is to provide a bifunctional active peptide having both ACE and DPP-IV inhibitory activity and a preparation method and application thereof, so as to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] One of the technical solutions of the present invention is a bifunctional active peptide having both ACE and DPP-IV inhibitory activities, the amino acid sequence of which is shown in SEQ ID NO.1.

[0007] The second technical solution of the present invention is a method for preparing the bifunctional active peptide having both ACE and DPP-IV inhibitory activities, comprising the following steps:

[0008] (1) enzymatically hydrolyzing sea cucumber intestinal eggs using aminopeptidase and proline endo-enzyme to obtain sea cucumber intestinal egg enzymatic hydrolysis products;

[0009] (2) After the sea cucumber intestinal egg hydrolysate is subjected to ultrafiltration and desalting treatment, the peptide sequences in the sea cucumber intestinal egg hydrolysate are identified by LC-MS / MS liquid chromatography-mass spectrometry to construct a peptide database of the sea cucumber intestinal egg hydrolysate, and obtain an enzymatic hydrolysate containing the bifunctional active peptide having both ACE and DPP-IV inhibitory activity;

[0010] (3) Screen and identify bifunctional active peptides with both ACE and DPP-IV inhibitory activities.

[0011] The third technical solution of the present invention is the use of the bifunctional active peptide having both ACE and DPP-IV inhibitory activity in the preparation of ACE inhibitors and / or DPP-IV inhibitors.

[0012] A fourth technical solution of the present invention is an ACE inhibitor comprising the bifunctional active peptide having both ACE and DPP-IV inhibitory activities.

[0013] The fifth technical solution of the present invention is a DPP-IV inhibitor, comprising the bifunctional active peptide having both ACE and DPP-IV inhibitory activities.

[0014] The sixth technical solution of the present invention is the use of the bifunctional active peptide having both ACE and DPP-IV inhibitory activity in the preparation of drugs for lowering blood pressure and / or blood sugar.

[0015] The seventh technical solution of the present invention is a drug for lowering blood pressure and / or blood sugar, comprising the bifunctional active peptide having both ACE and DPP-IV inhibitory activity.

[0016] Based on the above technical solution, the present invention has the following technical effects:

[0017] The present invention prepares and identifies a novel bifunctional active peptide with both ACE and DPP-IV inhibitory activity from sea cucumber enzymatic hydrolysate. This peptide not only inhibits ACE activity but also exhibits DPP-IV inhibitory activity, alleviating both hypertension and type 2 diabetes. Its bifunctionality makes it valuable for use in the preparation of products with both blood pressure and blood sugar lowering properties. The active peptide of the present invention significantly inhibits ACE activity while also exhibiting DPP-IV inhibitory activity. It has a simple structure, is safe, and exhibits strong activity. It can play a role in nutrition and health care, and is expected to provide an effective active ingredient for the development of foods and products with side effects that lower blood pressure, lower blood sugar, or both blood pressure and blood sugar, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0019] Figure 1 This is the amino acid structure and sequence secondary mass spectrometry identification diagram of a new bifunctional active peptide with both ACE and DPP-IV inhibitory activity.

[0020] Figure 2 This is a graph showing the inhibition rate of ACE at different concentrations by FPGGPP, a new bifunctional active peptide with both ACE and DPP-IV inhibitory activity.

[0021] Figure 3 Schematic diagram of the three-dimensional conformation of FPGGPP, a novel bifunctional active peptide with both ACE and DPP-IV inhibitory activity, docking with ACE.

[0022] Figure 4 This is a two-dimensional schematic diagram of the docking interaction between FPGGPP, a new bifunctional active peptide with both ACE and DPP-IV inhibitory activity, and ACE.

[0023] Figure 5 This is a graph showing the inhibition rate of FPGGPP, a new bifunctional active peptide with both ACE and DPP-IV inhibitory activity, on DPP-IV at different concentrations.

[0024] Figure 6 This is a schematic diagram of the three-dimensional conformation of the docking of FPGGPP, a new bifunctional active peptide with both ACE and DPP-IV inhibitory activity, with DPP-IV.

[0025] Figure 7 for Figure 6 Enlarged view of the boxed portion.

[0026] Figure 8 This is a two-dimensional schematic diagram of the docking interaction between FPGGPP, a new bifunctional active peptide with both ACE and DPP-IV inhibitory activity, and DPP-IV. DETAILED DESCRIPTION

[0027] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0028] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0029] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0030] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the present invention. The present description and examples are intended to be illustrative only.

[0031] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0032] Unless otherwise specified, the technical solutions described in the present invention are all conventional solutions in the field, and the reagents or raw materials used, unless otherwise specified, are purchased from commercial channels or have been disclosed.

[0033] An embodiment of the present invention provides a bifunctional active peptide having both ACE and DPP-IV inhibitory activities, the amino acid sequence of which is shown in SEQ ID NO.1.

[0034] The present invention also provides a method for preparing the bifunctional active peptide having both ACE and DPP-IV inhibitory activities, comprising the following steps:

[0035] (1) enzymatically hydrolyzing sea cucumber intestinal eggs using aminopeptidase and proline endo-enzyme to obtain sea cucumber intestinal egg enzymatic hydrolysis products;

[0036] (2) After the sea cucumber intestinal egg hydrolysate is subjected to ultrafiltration and desalting treatment, the peptide sequences in the sea cucumber intestinal egg hydrolysate are identified by LC-MS / MS liquid chromatography-mass spectrometry to construct a peptide database of the sea cucumber intestinal egg hydrolysate, and obtain an enzymatic hydrolysate containing the bifunctional active peptide having both ACE and DPP-IV inhibitory activity;

[0037] (3) Screen and identify bifunctional active peptides with both ACE and DPP-IV inhibitory activities.

[0038] In some specific embodiments, the enzymatic hydrolysis conditions are: the amount of the aminopeptidase used is 600 U / g, the amount of the proline endonuclease used is 1200 U / g,

[0039] The dosage of the sea cucumber intestinal egg substrate is 8% (v / v),

[0040] The enzymatic hydrolysis was carried out at 55℃ for 24 h and the pH value was 7.5.

[0041] In some specific embodiments, the screening method comprises: identifying the molecular weight of peptides in the sea cucumber intestinal egg enzymatic hydrolysate, and screening peptide sequences with a molecular weight less than 1 kDa to form a peptide database of sea cucumber intestinal egg enzymatic hydrolysate;

[0042] The DeltaM tool, PeptideRanker functional activity predictor, and Toixinpred safety and toxicity evaluation predictor were further used to predict the ACE and DPP-IV inhibitory activity and function of the peptides, and based on the functional scores, the bifunctional active peptides with both ACE and DPP-IV inhibitory activity were screened.

[0043] The embodiments of the present invention also provide the use of the bifunctional active peptide having both ACE and DPP-IV inhibitory activity in the preparation of ACE inhibitors and / or DPP-IV inhibitors.

[0044] The present invention also provides an ACE inhibitor comprising the bifunctional active peptide having both ACE and DPP-IV inhibitory activities.

[0045] An embodiment of the present invention further provides a DPP-IV inhibitor comprising the bifunctional active peptide having both ACE and DPP-IV inhibitory activities.

[0046] The embodiments of the present invention also provide the use of the bifunctional active peptide having both ACE and DPP-IV inhibitory activity in the preparation of drugs for lowering blood pressure and / or blood sugar.

[0047] An embodiment of the present invention further provides a drug for lowering blood pressure and / or blood sugar, comprising the bifunctional active peptide having both ACE and DPP-IV inhibitory activities.

[0048] The novel bifunctional active peptide provided by the present invention, which has both ACE and DPP-IV inhibitory activity, can not only significantly inhibit the activity of ACE, but also effectively inhibit the activity of DPP-IV, playing a role in preventing or even alleviating diseases such as hypertension and hyperglycemia, and is of great significance to the practical production and theoretical research of multifunctional active peptides.

[0049] Example 1

[0050] Preparation of active peptides from sea cucumber intestinal eggs

[0051] After washing and homogenization, sea cucumber intestinal eggs were subjected to a combined enzymatic hydrolysis using aminopeptidase and endoproline. The aminopeptidase and endoproline dosages were 600 U / g and 1200 U / g, respectively, with an 8% (v / v) sea cucumber intestinal egg substrate. The hydrolysis was performed at 55°C for 24 h, and the pH of the hydrolysis system was continuously monitored and adjusted to 7.5. The final product of the sea cucumber intestinal egg hydrolysis was ultrafiltered and desalted using a solid-phase extraction cartridge (SEP-PAK C18, Waters, USA) to prepare a sea cucumber intestinal egg hydrolysate containing active peptides. The molecular weights and sequences of the peptides prepared from the sea cucumber intestinal egg hydrolysate were determined using LC-MS / MS. Peptides with molecular weights less than 1 kDa were selected to form a peptide database of sea cucumber intestinal egg hydrolysates.

[0052] Example 2

[0053] Screening and mining of active peptide FPGGPP with ACE inhibitory activity

[0054] The peptide molecular weights and sequences of the obtained sea cucumber intestinal egg hydrolysates were identified by LC-MS / MS liquid chromatography-mass spectrometry, and peptide sequences with a molecular weight of less than 1 kDa were selected to form a peptide database, totaling 1876 entries. The DeltaM tool, PeptideRanker functional activity predictor, and Toixinpred safety and toxicity evaluation predictor were further used to predict the ACE and DPP-IV inhibitory activity and function of the peptides. Based on the functional scores, active peptides with potential ACE and DPP-IV inhibitory activity were screened and their secondary mass spectrometry structures were analyzed to obtain the amino acid sequences and structures of the active peptides.

[0055] The results are as follows Figure 1 As shown, the secondary mass spectrum of the active peptide obtained by screening shows that the amino acid sequence and arrangement of the active peptide are SEQ ID NO.1: FPGGPP.

[0056] Example 3

[0057] Verification of ACE inhibitory activity of active peptide FPGGPP

[0058] The ACE inhibitory activity of the active peptide FPGGPP was determined using a visible spectrophotometer in a 96-well plate. ACE inhibition was determined using 1 mM N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPPG) as a substrate, 0.1 U / mL angiotensin-converting enzyme (ACE), and HEPES as a buffer matrix (1.901 g HEPES reagent and 1.755 g NaCl reagent were dissolved in an appropriate amount of deionized water, and the buffer was adjusted to pH 8.3 with NaOH solution and the volume was made up to 100 mL for later use).

[0059] The assay steps are as follows: different concentrations of active peptide FPGGPP samples, as well as FAPPG substrate, ACE and buffer were added to a 96-well plate in sequence; the absorbance of the sample system at 340 nm was measured using a microplate reader and recorded; the sample system was placed in a shaker at 37°C for 30 minutes, and the absorbance of the sample system after reaction was measured again at 340 nm using a microplate reader; the ACE inhibition rate of the sample was determined by calculating the change in absorbance before and after the reaction.

[0060] The calculation formula is:

[0061] ACE inhibition rate of the sample (%) = 1-change in sample absorbance value / change in blank absorbance value.

[0062] The results are as follows Figure 2 As shown, when the active peptide FPGGPP concentration was 10 μg / mL, the inhibition rate of the active peptide FPGGPP against ACE was 18.4%; when the active peptide FPGGPP concentration was 25 μg / mL, the inhibition rate was 50.02%; when the active peptide FPGGPP concentration was 50 μg / mL, the inhibition rate was 97.4%; and when the active peptide FPGGPP concentration was 100 μg / mL, the inhibition rate was 103.2%. As the concentration of the active peptide FPGGPP continued to increase, the inhibition rate against ACE reached 100%. Furthermore, according to the results of the ACE inhibitory activity assay, the active peptide FPGGPP can completely inhibit ACE when the concentration is greater than 50 μg / mL. These results demonstrate that the active peptide FPGGPP has an effective ACE inhibitory effect.

[0063] Example 4

[0064] Molecular simulation docking of active peptide FPGGPP and ACE

[0065] The active peptide FPGGPP was docked with ACE by molecular simulation to further determine the mechanism of action of the active peptide in exerting its ACE inhibitory activity. Discovery studio software was used to draw a three-dimensional conformational map of the active peptide FPGGPP, and molecular simulation docking was performed with the catalytic active center of ACE (PDB: 1o8a). Based on the docking results, the interaction force between the active peptide FPGGPP and the key amino acid residues in the ACE active center was analyzed.

[0066] The results are as follows Figure 3 As shown in the figure, the active peptide FPGGPP can bind tightly to the active center of ACE and can be simulated and docked within the normal analysis time. The active peptide FPGGPP interacts with multiple amino acid residues in the active center of ACE, and the main amino acid residues are Phe527, Try520, Val518, Phe457, Glu411, His387, Glu384, Gln281, Trp279, Ala354, Ser355, Ala356, Glu376, His410, His353, Zn 2+ .

[0067] The results of the interaction analysis between the active peptide FPGGPP and the amino acid residues in the active center of ACE are as follows: Figure 4 As shown. The active peptide FPGGPP forms 4 hydrogen bond forces with ACE, 5 interactions between alkyl groups, 1 π-π interaction force, 4 carbon-hydrogen forces, and Zn 2+ Combination effect.

[0068] In summary, the active peptide FPGGPP can bind to ACE mainly through hydrogen bonds, hydrophobic interactions and Zn 2+ The binding effect interacts with the active center residues of ACE and thus inhibits the activity of ACE. That is, from the perspective of molecular simulation docking, it is further proved that the active peptide FPGGPP has significant ACE inhibitory activity.

[0069] Example 5

[0070] Verification of DPP-IV inhibitory activity of active peptide FPGGPP

[0071] The DPP-IV inhibitory activity of the active peptide FPGGPP was determined using a 96-well plate. The DPP-IV inhibition rate was determined using 1.6 mM Gly-Pro-pNA as the substrate, 0.1 U / mL DPP-IV, and Tris-HCl as the buffer (100 mM, pH 8.0).

[0072] The determination steps are as follows: different concentrations of active peptide FPGGPP samples, as well as Gly-Pro-pNA substrate, DPP-IV and buffer were added to a 96-well plate in sequence; the sample system was incubated at 37°C for 60 min and the reaction was terminated. The absorbance value of the sample system at 504 nm was measured using a microplate reader and recorded, and the DPP-IV inhibition rate was calculated according to the calculation formula.

[0073] The calculation formula is:

[0074] ;

[0075] Among them, A, B, C, and D are the absorbance values ​​of the sample group, control group, sample blank group, and blank group at 504 nm, respectively.

[0076] The results are as follows Figure 5 As shown, when the concentration of the active peptide FPGGPP was 100 μg / mL, the inhibition rate of the active peptide FPGGPP against DPP-IV was 19.96%; when the concentration of the active peptide FPGGPP was 200 μg / mL, the inhibition rate against DPP-IV was 52.08%; when the concentration of the active peptide FPGGPP was 400 μg / mL, the inhibition rate against DPP-IV was 82.87%; and when the concentration of the active peptide FPGGPP was 800 μg / mL, the inhibition rate against DPP-IV was 98.25%. According to the results of the DPP-IV inhibitory activity assay, the active peptide FPGGPP has effective DPP-IV inhibitory activity.

[0077] Example 6

[0078] Molecular simulation docking of active peptide FPGGPP and DPP-IV

[0079] The active peptide FPGGPP was docked with DPP-IV through molecular modeling to further determine the mechanism of action of the active peptide in exerting its DPP-IV inhibitory activity. Discovery studio software was used to draw a three-dimensional conformational map of the active peptide FPGGPP, and molecular modeling docking was performed with the catalytic active center of DPP-IV (PDB: 2QT9). Based on the docking results, the interaction force between the active peptide FPGGPP and the key amino acid residues in the DPP-IV active center was analyzed.

[0080] The results are as follows Figure 6 and Figure 7As shown, the active peptide FPGGPP can tightly bind to the DPP-IV active center, allowing for simulated docking within normal analysis time. Furthermore, the active peptide FPGGPP interacts with multiple amino acid residues in the DPP-IV active center, with the main amino acid residues being Arg471, Ser458, Tyr456, Val558, Arg560, and Val459.

[0081] The results of the interaction force analysis between the active peptide FPGGPP and the amino acid residues of the DPP-IV active center are as follows Figure 8 As shown in Figure 2, the active peptide FPGGPP forms four hydrogen bonds, four Van der Waals forces, and one salt bridge with DPP-IV.

[0082] In summary, the active peptide FPGGPP can bind to DPP-IV and inhibit DPP-IV activity by interacting with DPP-IV active center residues mainly through hydrogen bonds, Wandwala forces, and salt bridges. This further proves that the active peptide FPGGPP has significant DPP-IV inhibitory activity from the perspective of molecular simulation docking.

[0083] In summary, the present invention prepared and identified a novel bifunctional active peptide FPGGPP with both ACE and DPP-IV inhibitory activity from sea cucumber intestinal eggs through a complex enzyme hydrolysis method. The present invention obtained the amino acid sequence and structure of the active peptide by secondary mass spectrometry analysis, verified the inhibitory activity of the active peptide FPGGPP against ACE and DPP-IV, and demonstrated its inhibitory mechanism against ACE and DPP-IV activity by docking the active peptide FPGGPP with the active centers of ACE and DPP-IV, respectively, through molecular modeling docking.

[0084] The present invention provides a novel bifunctional active peptide FPGGPP with both ACE and DPP-IV inhibitory activity, which has significant ACE inhibitory activity and DPP-IV inhibitory activity.

[0085] Obviously, the above embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention and are not intended to limit the implementation methods of the present invention. A person skilled in the art will be able to make other variations or modifications based on the above description. It is not necessary and impossible to enumerate all implementation methods here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. A bifunctional active peptide having both ACE and DPP-IV inhibitory activity, characterized in that: Its amino acid sequence is shown in SEQ ID NO.

1.

2. The method for preparing a bifunctional active peptide having both ACE and DPP-IV inhibitory activities as claimed in claim 1, characterized in that: The following steps are involved: (1) Using aminopeptidase and proline endonuclease to enzymatically hydrolyze sea cucumber intestinal eggs to obtain sea cucumber intestinal egg enzymatic hydrolysis products; The enzymatic hydrolysis conditions are as follows: the amount of aminopeptidase used is 600 U / g, the amount of proline endonuclease used is 1200 U / g, The dosage of the sea cucumber intestine eggs is 8% (v / v), The enzymatic hydrolysis was carried out at 55 °C for 24 h, and the pH value was 7.5; (2) The sea cucumber intestinal egg hydrolysate was subjected to ultrafiltration and desalting treatment to obtain the sea cucumber intestinal egg hydrolysate containing the bifunctional active peptide with both ACE and DPP-IV inhibitory activity, and the sequence and molecular weight of the peptides in the sea cucumber intestinal egg hydrolysate were identified by LC-MS / MS liquid chromatography-mass spectrometry, and the peptide sequences with a molecular weight of less than 1 kDa were screened to form a peptide database of the sea cucumber intestinal egg hydrolysate; the DeltaM tool, the PeptideRanker functional activity predictor, and the Toixinpred safety and toxicity evaluation predictor were further used to predict the ACE and DPP-IV inhibitory activity and function of the peptides, and based on the functional score, the bifunctional active peptide with both ACE and DPP-IV inhibitory activity was screened.

3. An ACE inhibitor, characterized in that The invention comprises the bifunctional active peptide having both ACE and DPP-IV inhibitory activities as claimed in claim 1.

4. A DPP-IV inhibitor, characterized in that The invention comprises the bifunctional active peptide having both ACE and DPP-IV inhibitory activities as claimed in claim 1.

5. Use of the bifunctional active peptide having both ACE and DPP-IV inhibitory activities as claimed in claim 1 in the preparation of a drug for lowering blood pressure and / or blood sugar.

6. A drug for lowering blood pressure and / or blood sugar, characterized in that: The invention comprises the bifunctional active peptide having both ACE and DPP-IV inhibitory activities as claimed in claim 1.

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