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Polypeptide and derivative and hydrogel thereof, and application of polypeptide and derivative and hydrogel in preparation of medicine for preventing and/or treating type I diabetes mellitus

A technology of derivatives and hydrogels, applied in the field of application of polypeptides and their derivatives and hydrogels, in the preparation of drugs for the prevention and/or treatment of type I diabetes, can solve problems such as difficult to achieve ideal results in clinical applications, Achieve good blood sugar load, clear product chemical structure, and reduce the effect of morbidity

Active Publication Date: 2021-02-12
NANKAI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current intensive insulin therapy program injects or uses an insulin pump according to an established algorithm, which can establish a simulated physiological secretion mode of continuous subcutaneous insulin infusion (CSII), but it is still difficult to achieve the ideal effect in clinical application

Method used

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  • Polypeptide and derivative and hydrogel thereof, and application of polypeptide and derivative and hydrogel in preparation of medicine for preventing and/or treating type I diabetes mellitus
  • Polypeptide and derivative and hydrogel thereof, and application of polypeptide and derivative and hydrogel in preparation of medicine for preventing and/or treating type I diabetes mellitus
  • Polypeptide and derivative and hydrogel thereof, and application of polypeptide and derivative and hydrogel in preparation of medicine for preventing and/or treating type I diabetes mellitus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] (1) Peptide derivative Nap-G D f D f D Synthesis of Y

[0072] This embodiment provides a polypeptide whose sequence is shown in SEQ ID NO: 1 (Gly-D-Phe-D-Phe-D-Tyr, Gly-D-Phe-D-Phe-D-Tyr, G D f D f D The derivative of Y), its structural formula is:

[0073]

[0074] In the derivative, 2-naphthylacetic acid (Nap) is connected to the N-terminus of the polypeptide as a capping group to generate a derivative with a D configuration. For the convenience of description, the D configuration of the derivative is described as Nap-G in the present invention D f D f D Y.

[0075] The polypeptide derivative Nap-G of the present embodiment D f D f D Y was synthesized by Fmoc-short peptide solid-phase synthesis method. Specific steps are as follows:

[0076] 1) Weigh 0.5mmol 2-Cl-Trt resin in a solid-phase synthesizer, add 10mL of anhydrous dichloromethane (hereinafter referred to as DCM), place on a shaker and shake for 5min to fully swell the 2-Cl-Trt resin ;

[...

Embodiment 2

[0088] (1) Synthesis of polypeptide derivative Nap-GFFY

[0089] This embodiment provides a derivative of the polypeptide (Gly-Phe-Phe-Tyr, GFFY) whose sequence is shown in SEQ ID NO: 1, and its structural formula is:

[0090]

[0091] In the derivative, 2-naphthylacetic acid (Nap) is connected to the N-terminus of the polypeptide as a capping group to generate a derivative with an L configuration. For the convenience of description, the derivative is described as Nap-GFFY or Nap-G in the present invention L f L f L Y.

[0092] The polypeptide derivative Nap-GFFY of this example was synthesized by Fmoc-short peptide solid-phase synthesis method. Specific steps are as follows:

[0093] 1) Weigh 0.5mmol 2-Cl-Trt resin in a solid-phase synthesizer, add 10mL of anhydrous dichloromethane (hereinafter referred to as DCM), place on a shaker and shake for 5min to fully swell the 2-Cl-Trt resin ;

[0094] 2) Remove the DCM from the solid-phase synthesizer equipped with 2-Cl-T...

Embodiment 3

[0105] (1) Peptide derivative Nap- D f D Synthesis of F

[0106] This embodiment provides a polypeptide (D-Phe-D-Phe, D f D F) derivative, its structural formula is: And prepare the short peptide Nap- D f D F.

[0107] (2) Take 0.5mg Nap- D f D F was placed in a 1.5 ml glass bottle, added 500 microliters of PBS solution (pH=7.4), adjusted its pH value to 7.4 with sodium carbonate solution, heated to boiling to dissolve the compound completely, and cooled to room temperature to obtain Nap- D f D F short peptide hydrogel pharmaceutical preparations.

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Abstract

The invention belongs to the field of medicines and pharmacy, and provides a polypeptide, a derivative and hydrogel thereof, and an application of the polypeptide in preparation of medicines for preventing and / or treating type I diabetes mellitus. The invention provides a polypeptide of which the sequence is shown as SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3, and provides a derivative of the polypeptide and hydrogel thereof. The polypeptide, the derivative thereof and the hydrogel provided by the invention are simple in preparation process, the chemical structure of the product is clear, theused raw materials are amino acids necessary for a human body every day, the cost is low, and the biocompatibility is good; the polypeptide, the derivative thereof and the hydrogel can simulate insulin antigen epitopes, recover the immune tolerance to insulin antigens, have high ability to remove blood sugar, keep blood sugar stable in a normal range, and can effectively reduce the incidence of type I diabetes mellitus.

Description

technical field [0001] The invention relates to the fields of medicine and pharmacy, in particular to a polypeptide, its derivatives and hydrogel, and its application in the preparation of drugs for preventing and / or treating type I diabetes. Background technique [0002] Diabetes is one of the biggest public health events in the world in the 21st century. According to the latest statistics in 2015, a total of 415 million adults in the world suffer from diabetes, among which the number of diabetic patients in my country exceeds 100 million, accounting for about 10% of the total population of the country. Globally, the incidence of type 1 diabetes is increasing year by year, with an increase of about 2-3% per year. According to data reports, in the past 20 years in China, the incidence of diabetes has shown a trend of rejuvenation, and the incidence of diabetes in children and adolescents under the age of 15 has increased by nearly 4 times. Due to the serious complications ...

Claims

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Application Information

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IPC IPC(8): C07K5/103C07K5/065C08J3/075A61K39/00A61K9/06A61P3/10C08L89/00
CPCC07K5/1008C07K5/06078C08J3/075A61K39/0008A61K9/06A61P3/10C08J2389/00
Inventor 杨志谋王玲王忠彦李宸刘默涵
Owner NANKAI UNIV
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