CN114349818A - Tripeptides with double-target glucose-reducing function and application thereof - Google Patents
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Abstract
The invention discloses tripeptides with a double-target blood sugar reducing function and application thereof. The tripeptide has the sequence characteristics of Xaa1-Pro-Xaa 2. Wherein Xaa1 comprises one of Val, Leu and Ile amino acids; xaa2 includes one of Asn and Gln amino acids. The tripeptide with the double-target blood sugar reducing function provided by the invention not only has stronger DPP-IV inhibition activity, but also has stronger activity of promoting liver glucose consumption, and a medicament prepared from the tripeptide with the double-target blood sugar reducing function can effectively treat and prevent type II diabetes through the two targets.
Description
Technical Field
The invention relates to the field of medicines and medicine, in particular to the field of prevention and treatment of type II diabetes, and specifically relates to tripeptides with a double-target blood sugar reducing function and application thereof.
Background
The incidence of diabetes has increased year by year and has become the third chronic disease that seriously threatens human health. Clinical medicines are often accompanied by side effects such as weight gain, hypoglycemia, gastrointestinal adverse reactions and the like, and the safety of long-term administration of the medicines is yet to be further verified. The active peptide is safe, easy to absorb and free of side effects, and is an excellent candidate substance for developing products with the function of reducing blood sugar.
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are one of the new targets for the treatment of type II diabetes. Endogenous incretin hormones can promote the secretion of insulin, thereby reducing blood sugar. However, endogenous incretins are degraded by DPP-IV and lose their physiological activity. Therefore, the DPP-IV activity is inhibited, the generation of insulin can be promoted, and the hyperglycemia of diabetes mellitus can be reduced. The structural effect research of DPP-IV inhibitory peptide shows that: DPP-IV inhibitory peptides typically contain branched chain amino acids (Ile, Leu, and Val) at the N-terminus and a Pro residue at position P2.
The liver is one of the important organs for maintaining blood sugar balance in vivo. The liver promotes glucose uptake and glycogen synthesis by inhibiting gluconeogenesis, increases glucose consumption, and reduces the glucose content in blood. The existing research shows that amino acid not only exerts nutritive value in vivo, but also can be used as a signal factor to regulate the metabolic balance in vivo, such as glycometabolism balance. Amide amino acids are key nutrients that affect cellular metabolism. Glutamine and asparagine not only serve as important providers of cell nitrogen sources, but also serve as providers of key intermediate metabolites in the tricarboxylic acid cycle, so that the normal operation of the tricarboxylic acid cycle is ensured, the mitochondrial energy metabolism of cells is promoted, and the power is provided for the metabolism of glucose. Therefore, the peptide containing an amide-based amino acid has an effect of promoting glucose energy metabolism.
The combination of drugs from different hypoglycemic pathways is a common strategy for the clinical treatment of type II diabetes, with the most common mode of administration being the combination of a DPP-IV inhibitor and metformin. The DPP-IV inhibitor mainly has the activity of inhibiting DPP-IV, and the metformin mainly has the effect of reducing blood sugar by regulating and controlling the metabolic balance of liver sugar. The combination of these two drugs has achieved clinically good results. However, the combination of drugs not only increases the cost, but also has poor patient compliance (Dilingli; Luli; Leyan; Ficus auriculata, clinical efficacy of the dipeptidyl peptidase 4 inhibitor in combination with metformin for the treatment of type 2 diabetes mellitus. Utility drugs and clinics 2016,19, (09), 1094-.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide tripeptides with double-target glucose-reducing function and application thereof.
The tripeptide with the double-target hypoglycemic function provided by the invention is a hypoglycemic peptide with the double-target function, and the hypoglycemic peptide can inhibit DPP-IV activity and promote liver glucose consumption, thereby effectively preventing and treating type II diabetes.
The purpose of the invention is realized by at least one of the following technical solutions.
The tripeptide with the double-target blood sugar reducing function has the sequence of Xaa1-Pro-Xaa 2. Xaa1 is represented by a branched chain amino acid, and Xaa2 is represented by an amide amino acid.
The second position of the N end of the amino acid sequence of the tripeptide with the double-target blood sugar reducing function provided by the invention is Pro residue; the third position of the N end of the amino acid sequence is amide amino acid.
Furthermore, the first position of the N end of the amino acid sequence of the tripeptide with the double-target glucose-reducing function is branched chain amino acid; the branched chain amino acid is Ile, Val or Leu.
Further, the amide amino acid is Gln or Asn.
Furthermore, the tripeptide with double-target glucose-reducing function is shown in SEQ ID NO.1, and the amino acid sequence can be Ile-Pro-Gln.
Furthermore, the tripeptide with double-target sugar-reducing function is shown in SEQ ID NO.2, and the amino acid sequence can also be Leu-Pro-Gln.
Furthermore, the tripeptide with double-target sugar-reducing function is shown in SEQ ID NO.3, and the amino acid sequence can also be Val-Pro-Gln.
Furthermore, the tripeptide with double-target sugar-reducing function is shown in SEQ ID NO.4, and the amino acid sequence can also be Ile-Pro-Asn.
Furthermore, the tripeptide with double-target sugar-reducing function is shown in SEQ ID NO.5, and the amino acid sequence can also be Leu-Pro-Asn.
Furthermore, the tripeptide with double-target sugar-reducing function is shown in SEQ ID NO.5, and the amino acid sequence can also be Val-Pro-Asn.
The invention provides an application of tripeptides with double-target blood sugar reducing function in preparing a medicament for preventing and treating type II diabetes.
The tripeptides with the double-target-point blood sugar reducing function provided by the invention are obtained by reasonable design according to the structure-activity relationship of DPP-IV inhibitory peptide and the activity of special amino acid in liver glucose consumption; wherein the polypeptide with the second position as Pro residue has stronger DPP-IV inhibition activity, the first position at the N end is branched chain amino acid, especially DPP-IV activity of the peptide of Ile and Val is stronger relative to the activity of other peptides; meanwhile, the amide amino acids, Asn and Gln have stronger activity of promoting the glucose consumption of the liver. Therefore, the invention designs a tripeptide (shown by reference figure 3) with the sequence characteristics of Xaa1-Pro-Xaa2, wherein Xaa1 is Ile, Leu and Val, and Xaa2 is Asn and Gln. The tripeptide has DPP-IV (dipeptidyl peptidase IV) inhibiting activity and glucose consumption promoting activity, and can effectively treat and prevent type II diabetes through double targets.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the tripeptide with the double-target glucose-reducing function provided by the invention simultaneously has two glucose-reducing effects of inhibiting DPP-IV activity and promoting liver glucose consumption; the DPP-IV inhibitor can inhibit the activity of DPP-IV so as to inhibit the degradation of endogenous incretin hormone, further promote the secretion of insulin, achieve the effect of reducing blood sugar, simultaneously promote the consumption and metabolism of glucose by liver, reduce the hyperglycemia of a diabetic patient, is safe, easy to absorb and free of side effects, and can be applied to the preparation of medicines for preventing and treating type II diabetes.
Drawings
FIG. 1 is a diagram showing the DPP-IV inhibitory activity of tripeptides having a double-target glucose-lowering function in the examples;
FIG. 2 is a graph showing the glucose consumption promoting activity of HepG2 cells by tripeptides having a dual-target glucose lowering function in examples;
FIG. 3 is a schematic diagram of the sequence structure of tripeptide with double-target glucose-reducing function in the example.
Detailed Description
Tripeptides having a dual-target hypoglycemic function, which are used in the following examples, were designed according to the present invention and artificially synthesized by gill chemical company ltd. The amino acid sequences of the tripeptide with double-target hypoglycemic function are respectively shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 and SEQ ID NO. 6; in the examples, the 6 kinds of tripeptides having the dual-target glucose-lowering function are respectively labeled as tripeptide 1 having the dual-target glucose-lowering function, tripeptide 2 having the dual-target glucose-lowering function, tripeptide 3 having the dual-target glucose-lowering function, tripeptide 4 having the dual-target glucose-lowering function, tripeptide 5 having the dual-target glucose-lowering function, and tripeptide 6 having the dual-target glucose-lowering function.
The following examples are presented to further illustrate the practice of the invention, but the practice and protection of the invention is not limited thereto. It is noted that the processes described below, if not specifically described in detail, are all realizable or understandable by those skilled in the art with reference to the prior art. The reagents or apparatus used are not indicated to the manufacturer, and are considered to be conventional products available by commercial purchase.
Example 1: DPP-IV inhibitory activity of tripeptide 1 (IPQ shown in SEQ ID NO. 1) with double-target glucose-reducing function
The DPP-IV inhibitory activity determination method is as follows: adding 80 μ L sample (tripeptide 1 with double-target glucose-reducing function, sequence shown in SEQ ID NO. 1) and 80 μ L0.5 mM substrate Gly-Pro-pNA into 96-well plate, mixing, incubating at 37 deg.C for 10min in enzyme labeling apparatus, adding 40 μ L DPP-IV enzyme solution with concentration of 12.5mU/mL (preheating at 37 deg.C for 3min), oscillating30s and read at 405nm every 2min for 120min to monitor pNA release. An equivalent volume of 100mM Tris-HCl buffer, pH 8.0, was used as a control in place of the sample. The reagent or the sample is prepared or diluted by adopting the Tris-HCl buffer solution. The absorbance values (as ordinate) are plotted against time (as abscissa) in a linear range (R)2>0.995) and then the DPP-IV inhibitory activity of the sample was calculated according to the following formula.
DPP-IV inhibition ratio (%) - (1-Slope)sample/Slopecontrol)*100％；
Wherein SlopesampleSlope, representing the set of samplescontrolRepresents the slope of the control group.
Example 2: DPP-IV inhibitory activity of tripeptide 2 (LPQ with sequence shown as SEQ ID NO. 2) with double-target glucose-reducing function
The DPP-IV inhibitory activity determination method is as follows: adding 80 mU L of sample (tripeptide 2 with double-target glucose-reducing function, the sequence is shown in SEQ ID NO. 2) and 80 mU L of 0.5mM substrate Gly-Pro-pNA into a 96-well plate, mixing uniformly, placing the mixture in a microplate reader, incubating the mixture for 10min at 37 ℃, adding 40 mU L of DPP-IV enzyme solution with the concentration of 12.5mU/mL (preheating for 3min at 37 ℃), oscillating for 30s, reading at 405nm, reading every 2min, and reading for 120min in total, thereby monitoring the release condition of the pNA. An equivalent volume of 100mM Tris-HCl buffer, pH 8.0, was used as a control in place of the sample. The reagent or the sample is prepared or diluted by adopting the Tris-HCl buffer solution. The absorbance values (as ordinate) are plotted against time (as abscissa) in a linear range (R)2>0.995) and then the DPP-IV inhibitory activity of the sample was calculated according to the following formula.
DPP-IV inhibition ratio (%) - (1-Slope)sample/Slopecontrol)*100％；
Wherein SlopesampleSlope, representing the set of samplescontrolRepresents the slope of the control group.
Example 3: DPP-IV inhibitory activity of tripeptide 3 (VPQ with sequence shown in SEQ ID NO. 3) with double-target glucose-reducing function
The DPP-IV inhibitory activity determination method is as follows: adding 80 μ L of sample (tripeptide 3 with double-target glucose-reducing function, the sequence is shown in SEQ ID NO. 3) and 80 μ L of 0.5mM substrate Gly-Pro-pNA into a 96-well plate, mixing uniformly, placing the mixture in a microplate reader, incubating the mixture for 10min at 37 ℃, adding 40 μ L of DPP-IV enzyme solution with the concentration of 12.5mU/mL (preheating for 3min at 37 ℃), oscillating for 30s, reading at 405nm, reading every 2min, and reading for 120min in total, thereby monitoring the release condition of the pNA. An equivalent volume of 100mM Tris-HCl buffer, pH 8.0, was used as a control in place of the sample. The reagent or the sample is prepared or diluted by adopting the Tris-HCl buffer solution. The absorbance values (as ordinate) are plotted against time (as abscissa) in a linear range (R)2>0.995) and then the DPP-IV inhibitory activity of the sample was calculated according to the following formula.
DPP-IV inhibition ratio (%) - (1-Slope)sample/Slopecontrol)*100％；
Wherein SlopesampleSlope, representing the set of samplescontrolRepresents the slope of the control group.
Example 4: DPP-IV inhibitory activity of tripeptide 4 (IPN shown in SEQ ID NO. 4) with double-target glucose-reducing function
The DPP-IV inhibitory activity determination method is as follows: adding 80 μ L of sample (tripeptide 4 with double-target glucose-reducing function, the sequence is shown in SEQ ID NO. 4) and 80 μ L of 0.5mM substrate Gly-Pro-pNA into a 96-well plate, mixing uniformly, placing the mixture in a microplate reader, incubating the mixture for 10min at 37 ℃, adding 40 μ L of DPP-IV enzyme solution with the concentration of 12.5mU/mL (preheating for 3min at 37 ℃), oscillating for 30s, reading at 405nm, reading every 2min, and reading for 120min in total, thereby monitoring the release condition of the pNA. An equivalent volume of 100mM Tris-HCl buffer, pH 8.0, was used as a control in place of the sample. The reagent or the sample is prepared or diluted by adopting the Tris-HCl buffer solution. The absorbance values (as ordinate) are plotted against time (as abscissa) in a linear range (R)2>0.995) and then the DPP-IV inhibitory activity of the sample was calculated according to the following formula.
DPP-IV inhibition ratio (%) - (1-Slope)sample/Slopecontrol)*100％；
Wherein SlopesampleSlope, representing the set of samplescontrolRepresents the slope of the control group.
Example 5: DPP-IV inhibitory activity of tripeptide 5 (LPN with sequence shown in SEQ ID NO. 5) with double-target glucose-reducing function
The DPP-IV inhibitory activity determination method is as follows: adding 80 μ L of sample (tripeptide 5 with double-target glucose-reducing function, the sequence is shown in SEQ ID NO. 5) and 80 μ L of 0.5mM substrate Gly-Pro-pNA into a 96-well plate, mixing uniformly, placing the mixture in a microplate reader, incubating the mixture for 10min at 37 ℃, adding 40 μ L of DPP-IV enzyme solution with the concentration of 12.5mU/mL (preheating for 3min at 37 ℃), oscillating for 30s, reading at 405nm, reading every 2min, and reading for 120min in total, thereby monitoring the release condition of the pNA. An equivalent volume of 100mM Tris-HCl buffer, pH 8.0, was used as a control in place of the sample. The reagent or the sample is prepared or diluted by adopting the Tris-HCl buffer solution. The absorbance values (as ordinate) are plotted against time (as abscissa) in a linear range (R)2>0.995) and then the DPP-IV inhibitory activity of the sample was calculated according to the following formula.
DPP-IV inhibition ratio (%) - (1-Slope)sample/Slopecontrol)*100％；
Wherein SlopesampleSlope, representing the set of samplescontrolRepresents the slope of the control group.
Example 6: DPP-IV inhibitory activity of tripeptide 6 (VPN with sequence shown as SEQ ID NO. 6) with double-target glucose-reducing function
The DPP-IV inhibitory activity determination method is as follows: adding 80 μ L of sample (tripeptide 6 with double-target glucose-reducing function, the sequence is shown in SEQ ID NO. 1) and 80 μ L of 0.5mM substrate Gly-Pro-pNA into a 96-well plate, mixing uniformly, placing the mixture in a microplate reader, incubating the mixture for 10min at 37 ℃, adding 40 μ L of DPP-IV enzyme solution with the concentration of 12.5mU/mL (preheating for 3min at 37 ℃), oscillating for 30s, reading at 405nm, reading every 2min, and reading for 120min in total, thereby monitoring the release condition of the pNA. An equivalent volume of 100mM Tris-HCl buffer, pH 8.0, was used as a control in place of the sample. The reagent or the sample is prepared or diluted by adopting the Tris-HCl buffer solution. Measuring the absorbance value of (As ordinate) versus time (as abscissa) in a linear range (R)2>0.995) and then the DPP-IV inhibitory activity of the sample was calculated according to the following formula.
DPP-IV inhibition ratio (%) - (1-Slope)sample/Slopecontrol)*100％；
Wherein SlopesampleSlope, representing the set of samplescontrolRepresents the slope of the control group.
From the tests of examples 1 to 6, the DPP-IV inhibitory activities of peptides at a final concentration of 200. mu.M were: IPQ 71.64%; LPQ is 50.75%; VPQ-64.21%; IPN 60.55%; LPN 40.69%; the VPN is 61.97%, as shown in fig. 1. The detection result shows that the tripeptide with the characteristic sequence of Xaa1-Pro-Xaa2 has stronger DPP-IV inhibitory activity.
Example 7: tripeptide 1 (IPQ shown in SEQ ID NO. 1) with double-target glucose-reducing function for promoting glucose consumption activity of HepG2 cells
The glucose consumption activity of HepG2 cells was determined as follows: taking cells in logarithmic growth phase at 1 × 105One/well inoculated in 96-well plates at 37 ℃ with 5% CO2The culture box is used for culturing for 24 hours. The medium was removed, 100. mu.L of the basal medium MEM (containing 5mM glucose) was added to the blank group, and 100. mu.L of the basal medium MEM (containing 5mM glucose and containing the tripeptide 1 having the dual-target glucose-lowering function at a final concentration of 400. mu.M) was added to the sample group, followed by incubation for 18 hours. And taking cell culture supernatant, and determining the content of the residual glucose in the cell culture medium by using a glucose oxidase kit. Cell concentration was determined using the MTT method. Glucose consumption was calculated by subtracting the glucose concentration in the cell culture medium after 18h incubation from the glucose concentration in the original medium. The glucose consumption of each group of cells was corrected using the cell concentration of each group.
Example 8: tripeptide 2 (LPQ with sequence shown in SEQ ID NO. 2) with double-target glucose-reducing function for promoting glucose consumption activity of HepG2 cells
The glucose consumption activity of HepG2 cells was determined as follows: taking cells in logarithmic growth phase at 1 × 105One/holeInoculating in 96-well plate at 37 deg.C and 5% CO2The culture box is used for culturing for 24 hours. The medium was removed, 100. mu.L of the basal medium MEM (containing 5mM glucose) was added to the blank group, and 100. mu.L of the basal medium MEM (containing 5mM glucose and containing the tripeptide 2 having the dual-target glucose-lowering function at a final concentration of 400. mu.M) was added to the sample group, followed by incubation for 18 hours. And taking cell culture supernatant, and determining the content of the residual glucose in the cell culture medium by using a glucose oxidase kit. Cell concentration was determined using the MTT method. Glucose consumption was calculated by subtracting the glucose concentration in the cell culture medium after 18h incubation from the glucose concentration in the original medium. The glucose consumption of each group of cells was corrected using the cell concentration of each group.
Example 9: tripeptide 3 (VPQ with sequence shown in SEQ ID NO. 3) with double-target glucose-reducing function for promoting glucose consumption activity of HepG2 cells
The glucose consumption activity of HepG2 cells was determined as follows: taking cells in logarithmic growth phase at 1 × 105One/well inoculated in 96-well plates at 37 ℃ with 5% CO2The culture box is used for culturing for 24 hours. The medium was removed, 100. mu.L of the basal medium MEM (containing 5mM glucose) was added to the blank group, and 100. mu.L of the basal medium MEM (containing 5mM glucose and containing the tripeptide 3 having a double-target glucose-lowering function at a final concentration of 400. mu.M) was added to the sample group, and the mixture was incubated for 18 hours. And taking cell culture supernatant, and determining the content of the residual glucose in the cell culture medium by using a glucose oxidase kit. Cell concentration was determined using the MTT method. Glucose consumption was calculated by subtracting the glucose concentration in the cell culture medium after 18h incubation from the glucose concentration in the original medium. The glucose consumption of each group of cells was corrected using the cell concentration of each group.
Example 10: tripeptide 4 with double-target glucose-reducing function (IPN with sequence shown in SEQ ID NO. 4) promotes glucose consumption activity of HepG2 cells
The glucose consumption activity of HepG2 cells was determined as follows: taking cells in logarithmic growth phase at 1 × 105One/well inoculated in 96-well plates at 37 ℃ with 5% CO2The culture box is used for culturing for 24 hours. The medium was removed and the blank was supplemented with 100. mu.L of minimal medium MEM (containing 5mM grape)Sugar), the sample group was incubated for 18 hours with 100. mu.L of a basal medium MEM (containing 5mM glucose and containing tripeptide 4 having a double-target glucose-lowering function at a final concentration of 400. mu.M). And taking cell culture supernatant, and determining the content of the residual glucose in the cell culture medium by using a glucose oxidase kit. Cell concentration was determined using the MTT method. Glucose consumption was calculated by subtracting the glucose concentration in the cell culture medium after 18h incubation from the glucose concentration in the original medium. The glucose consumption of each group of cells was corrected using the cell concentration of each group.
Example 11: tripeptide 5 with double-target glucose-reducing function (LPN with sequence shown in SEQ ID NO. 5) promotes glucose consumption activity of HepG2 cells
The glucose consumption activity of HepG2 cells was determined as follows: taking cells in logarithmic growth phase at 1 × 105One/well inoculated in 96-well plates at 37 ℃ with 5% CO2The culture box is used for culturing for 24 hours. The medium was removed, 100. mu.L of the basal medium MEM (containing 5mM glucose) was added to the blank group, and 100. mu.L of the basal medium MEM (containing 5mM glucose and containing tripeptide 5 having a double-target glucose-lowering function at a final concentration of 400. mu.M) was added to the sample group, followed by incubation for 18 hours. And taking cell culture supernatant, and determining the content of the residual glucose in the cell culture medium by using a glucose oxidase kit. Cell concentration was determined using the MTT method. Glucose consumption was calculated by subtracting the glucose concentration in the cell culture medium after 18h incubation from the glucose concentration in the original medium. The glucose consumption of each group of cells was corrected using the cell concentration of each group.
Example 12: tripeptide 6 (VPN with sequence shown as SEQ ID NO. 6) with double-target sugar-reducing function for promoting glucose consumption activity of HepG2 cells
The glucose consumption activity of HepG2 cells was determined as follows: taking cells in logarithmic growth phase at 1 × 105One/well inoculated in 96-well plates at 37 ℃ with 5% CO2The culture box is used for culturing for 24 hours. The medium was removed, 100. mu.L of the basal medium MEM (containing 5mM glucose) was added to the blank group, and 100. mu.L of the basal medium MEM (containing 5mM glucose and containing the tripeptide 6 having a double-target glucose-lowering function at a final concentration of 400. mu.M) was added to the sample group, followed by incubation for 18 hours. Get the thinCell culture supernatant, and determining the residual glucose content in the cell culture medium by using a glucose oxidase kit. Cell concentration was determined using the MTT method. Glucose consumption was calculated by subtracting the glucose concentration in the cell culture medium after 18h incubation from the glucose concentration in the original medium. The glucose consumption of each group of cells was corrected using the cell concentration of each group.
As shown in fig. 2, the results of the experiments of examples 7 to 12 showed that the glucose consumption of 400 μ M hypoglycemic peptides was significantly increased compared to the blank group, and the effect of increasing the glucose consumption of hypoglycemic peptides compared to the blank group was 14.23% IPQ; LPQ is 12.88%; VPQ 16.42%; IPN 16.50%; LPN 12.18%; VPN 22.85%. The results show that the tripeptide of the characteristic sequence Xaa1-Pro-Xaa2 provided by the invention can obviously promote the glucose consumption of liver cells.
The above examples are only preferred embodiments of the present invention, which are intended to be illustrative and not limiting, and those skilled in the art should understand that they can make various changes, substitutions and alterations without departing from the spirit and scope of the invention.
Sequence listing
<110> university of southern China's science
GUANGDONG HUATAI BIOLOGICAL TECHNOLOGY Co.,Ltd.
<120> tripeptides with double-target glucose-reducing function and application thereof
<160> 6
<170> SIPOSequenceListing 1.0
<210> 1
<211> 3
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 1
Ile Pro Gln
1
<210> 2
<211> 3
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 2
Leu Pro Gln
1
<210> 3
<211> 3
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 3
Val Pro Gln
1
<210> 4
<211> 3
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 4
Ile Pro Asn
1
<210> 5
<211> 3
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 5
Leu Pro Asn
1
<210> 6
<211> 3
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 6
Val Pro Asn
1
Claims (10)
1. Tripeptides with double-target sugar-reducing function are characterized in that the second position at the N end of an amino acid sequence is a Pro residue; the third position of the N end of the amino acid sequence is amide amino acid.
2. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the first position at the N-terminal of the amino acid sequence is a branched amino acid; the branched chain amino acid is Ile, Val or Leu.
3. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the amide amino acid is Gln or Asn.
4. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the amino acid sequence is Ile-Pro-Gln as shown in SEQ ID No. 1.
5. The tripeptide with double-target blood sugar reducing function according to claim 1, wherein the amino acid sequence is Leu-Pro-Gln as shown in SEQ ID NO. 2.
6. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the amino acid sequence is Val-Pro-Gln as shown in SEQ ID No. 3.
7. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the amino acid sequence is Ile-Pro-Asn as shown in SEQ ID No. 4.
8. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the amino acid sequence is Leu-Pro-Asn as shown in SEQ ID No. 5.
9. The tripeptide with double-target hypoglycemic function according to claim 1, wherein the amino acid sequence is Val-Pro-Asn as shown in SEQ ID No. 6.
10. Use of the tripeptide with double target point hypoglycemic function according to any one of claims 1 to 9 in the preparation of a medicament for the prevention and treatment of type ii diabetes.
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| 孙冠华: "乳源性生物活性小肽的巨噬细胞免疫功能特性研究", 中国优秀硕士学位论文全文数据库 基础科学辑, no. 2015, pages 006 - 36 * |
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