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GLP-1 receptor agonist and application thereof

A receptor agonist, GLP-1 technology, applied in the field of biomedicine, can solve the problems of short half-life and no new peptide sequence

Active Publication Date: 2021-10-01
HUNAN ZONSEN PEPLIB BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Existing GLP-1 receptor agonists are all modified based on the endogenous GLP-1 sequence. Currently, there is no new peptide sequence, and they are all linear GLP-1 analogs, which are easy to degrade in vivo and have a short half-life.

Method used

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  • GLP-1 receptor agonist and application thereof
  • GLP-1 receptor agonist and application thereof
  • GLP-1 receptor agonist and application thereof

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Experimental program
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Effect test

Embodiment 1

[0034] 1. Key reagents: polypeptide library (self-made), CHO cell (Chinese hamster ovarycell, Chinese hamster warm nest cell) line overexpressing GLP-1R, abbreviated as CHO-K1 / GLP-1R / Gα15 cell (Genscript), Calcium6Assay Kit (Molecular Devices).

[0035] 2. High-throughput screening process

[0036] 2.1. Cultivation of CHO-K1 / GLP1 / Gα15 cells

[0037] 2.1.1. Cell recovery: Take out the cells from the liquid nitrogen tank, and quickly thaw the cells in a 37°C water bath. Move the cells to a 15ml centrifuge tube, slowly add 9mL of preheated thawed medium, centrifuge at 800 rpm for 5 minutes, and remove the supernatant medium. The cells were resuspended with 5ml of thawed medium, transferred to a T25 culture flask, and cultured in an incubator at 37°C and 5% CO2. The next day after cell recovery, the medium was replaced with growth medium.

[0038] 2.1.2. Cell subculture: When the cells are 80-90% full of the culture flask, wash the cells with DPBS first, then digest the cells ...

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Abstract

The invention discloses a GLP-1 receptor agonist, and belongs to the field of biological medicine. according to the invention, a high-throughput drug screening technology is applied to screen the polypeptide named 100-44 (PL00201001) from a large cyclic peptide library, and the polypeptide can activate a GLP-1 receptor and cause activation of a cell signal channel. PL00201001 contains 80 amino acid cyclic peptides, a series of derived small cyclic peptides and linear peptides are obtained through a decompression technology, and both the small cyclic peptides and the linear peptides have the effect of a GLP-1 receptor agonist. The PL00201001 and a series of polypeptides thereof can be used as GLP-1 receptor agonists, and new polypeptide drugs for diabetes, obesity and related diseases thereof can be further developed.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a GLP-1 receptor agonist and application thereof. Background technique [0002] Protein-coupled receptors (G protein-coupled receptors, GPCRs) are a class of 7 transmembrane receptors, belonging to cell membrane surface receptors, accounting for about 4% of the encoded proteins in the human genome. There are about 475 targets of FDA-approved drugs, of which about 108 are GPCRs, accounting for 34%. The annual global sales of GPCRs receptor drugs exceed 180 billion US dollars, accounting for more than 27% of the global drug market. It can be seen that the development of GPCRs receptor drugs has broad prospects. [0003] Glucagon-like peptide 1 receptor (GLP-1R) is a class B GPCRs composed of 463 amino acids. GLP-1R is regulated by endogenous GLP-1 polypeptides including (GLP-1(1-36)NH 2 , GLP-1(7–36)NH2, GLP-1(1-37) and GLP-1(7-37) and regulation of exogenous poly...

Claims

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Application Information

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IPC IPC(8): C07K14/00A61K38/16A61P3/10A61P3/04
CPCC07K14/00A61P3/10A61P3/04A61K38/00
Inventor 王登刘惠清王珠银王新波李向群宫焕章张曾源王芹芹
Owner HUNAN ZONSEN PEPLIB BIOTECH CO LTD
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