Application of polypeptide as olfactory receptor Olfr109 antagonist ligand

A ligand and carrier technology, applied in the field of anti-metabolic disease drugs, can solve problems such as gastrointestinal discomfort, and achieve good specificity and cost-effective effects

Active Publication Date: 2020-11-13
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, commonly used hypoglycemic drugs in clinic, such as biguanides, thiazolidinediones and sulfonylureas, etc., although the short-term effic

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  • Application of polypeptide as olfactory receptor Olfr109 antagonist ligand
  • Application of polypeptide as olfactory receptor Olfr109 antagonist ligand
  • Application of polypeptide as olfactory receptor Olfr109 antagonist ligand

Examples

Experimental program
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Example Embodiment

[0034] Example 1 Polypeptide specifically antagonizes the downstream signaling pathway of Olfr109 and inhibits the function of Olfr109 Experimental steps:

[0035] 1. Use 431A peptide synthesizer (Perkin Elmer) to synthesize the following polypeptides:

[0036] Arg-Phe-Val-Ala-Ile-Cys-Ser-Pro-Leu-Arg-Tyr-Thr-Ala-Ile-Met

[0037] 2. The molecular biology method was used to construct the recombinant plasmid of Olfr109 with gene recombination, overexpress Olfr109 in HEK293 cells, and use the Glosensor method to detect the principle of the second messenger cAMP, and stimulate the cells to produce cAMP with the agonist of adenylyl cyclase Forskolin At the same time, the Olfr109 agonist InsB was stimulated, and the activation of the downstream Gi signaling pathway of Olfr109 was characterized by the degree of reduction in the intracellular cAMP concentration. The antagonism of the downstream Gi signaling pathway of Olfr109; the bioluminescence resonance energy transfer method of Ol...

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Abstract

The invention belongs to the technical field of anti-metabolic disease drugs, and particularly relates to application of polypeptide as an olfactory receptor Olrfr109 antagonist ligand. Existing researches show that the olfactory receptor Olfr109 plays an important role in maintaining the steady state of blood glucose and also has an influence on the insulin secretion level. The invention providesan antagonist ligand aiming at an olfactory receptor Olfr109 according to the research background. The polypeptide can inhibit downstream Gi through combination with Olfr109, and inhibit downstream Gi, beta-arrestin1 signal channel and a beta-arrestin2 signal channel through combination with Olfr109, and the can be used for preparing metabolic disease model drugs. The antagonist has the functionsof relieving insulin secretion disorders caused by excessive activation of the Olfr109 and promoting insulin secretion, and has popularization significance as a good clinical drug or research tool.

Description

technical field [0001] The disclosure belongs to the technical field of anti-metabolic disease drugs, and specifically relates to the application of a polypeptide as an olfactory receptor Olfr109 antagonist ligand and Gi, β-arrestin-1 and β-arrestin-2 signal pathway inhibitors. Background technique [0002] The information disclosed in this Background section is only intended to increase the understanding of the general background of the disclosure, and is not necessarily to be taken as an acknowledgment or any form of suggestion that the information constitutes prior art that is already known to those skilled in the art. [0003] Diabetes mellitus is a metabolic disease characterized by elevated blood sugar. Insufficient insulin secretion or insulin resistance is a key factor in the occurrence of diabetes. Currently commonly used hypoglycemic drugs in clinical practice, such as biguanides, thiazolidinediones, and sulfonylureas, have significant short-term efficacy, but long...

Claims

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Application Information

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IPC IPC(8): C07K7/08C12N15/11A61K38/10A61P3/04A61P3/10
CPCC07K7/08A61P3/04A61P3/10A61K38/00
Inventor 孙金鹏于晓程杰杨照
Owner SHANDONG UNIV
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