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CN-122011105-A - ACE (angiotensin converting enzyme) inhibitory peptide and application thereof

CN122011105ACN 122011105 ACN122011105 ACN 122011105ACN-122011105-A

Abstract

The invention provides ACE inhibitory peptide and application thereof, and belongs to the technical field of preparation of bioactive peptides. According to the invention, 6 polypeptides with ACE inhibitory activity are efficiently screened from royal jelly protein by using computer simulation guidance, and the amino acid sequence of the ACE inhibitory peptide is shown as any one of SEQ ID NO. 1-6. The ACE inhibitory peptide provided by the invention has the advantages of clear structure, clear source and remarkable ACE inhibitory activity, and is a novel food-borne ACE inhibitory peptide. Furthermore, the ACE inhibitory peptide derived from the royal jelly provided by the invention is safe, has no toxic or side effect, and can be developed as health-care food, food additives, drug synergists and the like.

Inventors

  • ZHANG BIN
  • ZHAO YUAN
  • YANG WANYU
  • FAN JINLING
  • ZHANG TIANRONG
  • DU LIN
  • ZOU XINYU
  • WANG BAO

Assignees

  • 河南科技大学

Dates

Publication Date
20260512
Application Date
20260403

Claims (10)

  1. 1. The ACE inhibitory peptide is characterized in that the amino acid sequence of the ACE inhibitory peptide is shown as any one of SEQ ID NO. 1-6.
  2. 2. The ACE inhibitory peptide according to claim 1, wherein the amino acid sequence of the ACE inhibitory peptide is shown in SEQ ID NO. 5.
  3. 3. The ACE inhibiting peptide according to claim 1 or 2, wherein the ACE inhibiting peptide is obtained by a process comprising the steps of: (1) Screening protease according to the computer simulated royal jelly proteolytic result, and adopting the protease obtained by screening to carry out enzymolysis on the royal jelly protein to obtain enzymolysis liquid; (2) And (3) separating and purifying the enzymolysis liquid obtained in the step (1), and obtaining ACE inhibitory peptide through liquid chromatography-tandem mass spectrometry analysis and peptide group screening.
  4. 4. The ACE inhibitory peptide of claim 3, wherein the protease selected in step (1) is bromelain.
  5. 5. The ACE inhibitory peptide according to claim 4, wherein the enzymolysis condition in the step (1) is that the enzyme addition amount is 5-6% of the substrate mass, and the enzymolysis is carried out for 1-2 hours under the conditions of pH 7.0-7.5 and 55-60 ℃.
  6. 6. The ACE inhibitory peptide of claim 5, wherein the royal jelly protein of step (1) is prepared by dissolving royal jelly in a buffer, separating the supernatant from solid-liquid, collecting the concentrate by ultrafiltration, and freeze-drying.
  7. 7. The ACE inhibitory peptide of claim 3, wherein the separation and purification in step (2) is performed by separating the enzymatic hydrolysate with an ultrafiltration membrane and purifying the separated and collected fraction with a gel chromatography column.
  8. 8. The ACE inhibitory peptide of claim 7, wherein the fraction collected by the separation has a molecular weight of less than 3kDa.
  9. 9. The ACE inhibitory peptide of claim 7, wherein the gel chromatography column is a Sephadex G-15 gel chromatography column.
  10. 10. The use of an ACE inhibiting peptide as claimed in any one of claims 1 to 9, wherein the use comprises any one of the following: (1) Preparing a preparation for inhibiting ACE activity; (2) Preparing a medicament for treating or preventing hypertension; (3) Preparing health products or functional foods with auxiliary blood pressure lowering function.

Description

ACE (angiotensin converting enzyme) inhibitory peptide and application thereof Technical Field The invention belongs to the technical field of preparation of bioactive peptides, and particularly relates to ACE (angiotensin converting enzyme) inhibitory peptide and application thereof. Background Hypertension is one of the most common chronic diseases worldwide, an important changeable risk factor leading to cardiovascular diseases, causing a great deal of premature death each year, and seriously threatening public health. Angiotensin Converting Enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS) and regulates blood pressure by catalyzing the production of angiotensin II from angiotensin I. Therefore, ACE has become an important pharmacological target for antihypertensive therapy. At present, the synthesized ACE inhibitors such as captopril, enalapril and the like which are commonly used clinically have remarkable curative effects, but often have adverse reactions such as cough, kidney function damage, rash and taste disorder. Therefore, the development of food-derived ACE inhibitory peptides with higher safety and lower side effects from natural food proteins has become a leading-edge hotspot for the development of functional foods and antihypertensive drugs. ACE is a zinc ion-containing carboxydipeptidase, the catalytic mechanism of which depends on the formation of coordination bonds between the zinc ion in the active center and the substrate, and the action mechanism of ACE inhibitory peptides is mainly divided into three types, competitive inhibition, non-competitive inhibition and mixed inhibition. Among them, most ACE inhibiting peptides act as competitive inhibitors, i.e. certain amino acid residues at the N-or C-terminus (e.g. tryptophan, tyrosine, phenylalanine, proline) form hydrogen bonds, hydrophobic interactions or electrostatic interactions with amino acid residues in the ACE active pocket, thus preventing the entry of the substrate into the catalytic site. From a structural point of view, the activity of ACE inhibitory peptides is closely related to their amino acid sequences. It is believed that peptide fragments containing aromatic amino acids (Phe, tyr, trp) or prolines at the C-terminus bind more readily to the S1, S2 subsites of ACE, while hydrophobic amino acids at the N-terminus help to enhance the binding stability of peptides to enzymes. In addition, peptide chain length is also a critical factor. Dipeptides and tripeptides tend to show higher inhibitory activity, as the short peptides can more flexibly adapt to the spatial conformation of the ACE active pocket. For example, dipeptides and tripeptides derived from bovine milk beta-lactoglobulin have been shown by several clinical studies to have an exact antihypertensive effect by a mechanism that plays a major inhibitory role by blocking the C domain of ACE. ACE inhibiting peptides are extremely widely available and cover almost all edible proteins. Milk protein is one of the sources which are studied by systems at the earliest time, casein and whey protein can release various high-activity ACE inhibitory peptides after enzymolysis, and fish protein, especially marine fish muscle protein such as bonito, sardine and the like, becomes an important source of the high-activity ACE inhibitory peptides due to unique amino acid composition. In the aspect of vegetable proteins, soy protein, zein, rice bran protein and the like can also produce peptide fragments with obvious antihypertensive activity after enzymolysis. In recent years, novel protein resources such as insect proteins, algae proteins and the like gradually enter a research field of view, and a novel direction is provided for raw material expansion of ACE inhibitory peptides. The royal jelly is secreted by the hypopharyngeal glands and the mandibular glands of the worker bees, the protein content of the royal jelly accounts for 30% -50% of the dry matter, and the main protein of the royal jelly is the main material basis of the biological activity of the royal jelly. However, the royal jelly protein has certain limitation in practical application, namely the royal jelly protein is easy to degrade and deactivate under normal temperature condition, needs whole-course cold chain storage and transportation, and has high industrialization cost, and meanwhile, the macromolecular protein has certain sensitization, partial people can have mild allergic reaction after taking the royal jelly protein, and the royal jelly has sour and astringent taste and poor palatability. To overcome these limitations, enzymolysis technology has been developed as a promising strategy to degrade royal jelly proteins into small-molecule peptide fragments, which not only helps to reduce sensitization, improve stability, but also may enhance their biological activity. Studies have reported that a number of peptides having Angiotensin Converting Enzyme (ACE) inhibitory activity, such as FRYR (I