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A kind of polypeptide compound targeting PD-1 receptor, its preparation method and application

A technology of peptide compounds and compounds, applied in the field of peptide compounds, can solve problems such as hindering applications, achieve the effects of easy purification, avoid opioid-related side effects, and improve pharmacological properties

Active Publication Date: 2022-06-03
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, opioids have been widely used in the clinical treatment of non-cancer chronic pain, but opioids inevitably cause drug tolerance, physical and mental dependence, gastrointestinal function inhibition, nausea, sedation, irritability, hallucinations, and Side effects such as motor function impairment are the main problems hindering its application in clinical treatment

Method used

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  • A kind of polypeptide compound targeting PD-1 receptor, its preparation method and application
  • A kind of polypeptide compound targeting PD-1 receptor, its preparation method and application
  • A kind of polypeptide compound targeting PD-1 receptor, its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0040] Weighing wang resin, dichloromethane swelling, anhydrous methanol compression, N,N-dimethylacetamide washing. preconditioned

[0043] The same operation as the resin pretreatment and the removal of the Fmoc group during the synthesis of compound 1. The N,N-diisopropylethyl

[0046] The same operation as the resin pretreatment and the removal of the Fmoc group during the synthesis of compound 1. in N,N-diisopropylethyl

[0049] The same operation as the resin pretreatment and the removal of the Fmoc group during the synthesis of compound 1. The N,N-diisopropylethyl

[0052] The same operation as the resin pretreatment and the removal of the Fmoc group during the synthesis of compound 1. The N,N-diisopropylethyl

[0056]

[0058]

Embodiment 2D

[0060] The inhibitory effect of compounds 1 to 5 on pain signaling is identified by DRG neuron calcium imaging technology.

Embodiment 3

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Abstract

The present invention discloses a class of polypeptide compounds targeting PD-1 receptors. The polypeptide compounds include compound 1, compound 2, compound 3, compound 4 and compound 5; wherein, the amino acid sequence of compound 1-5 is as shown in SEQ ID NO : as shown in 1‑5. The invention also discloses a preparation method of a polypeptide compound targeting the PD-1 receptor, including the following process: using solid-phase synthesis, sequentially coupling the amino acids of compound 1-5 to a solid-phase resin according to the peptide sequence Above, the target compound is obtained through cleavage reagent cleavage, freeze-drying, preparation and purification. The invention also discloses the application of a class of polypeptide compounds targeting PD‑1 receptors in the preparation of analgesic drugs. The small molecule polypeptide of the present invention: compounds 1-5 can bind to PD-1, and have significant inhibitory effects on inflammatory pain and visceral pain under intrathecal administration; and the synthesis is simple, easy to purify, and facilitates large-scale synthesis.

Description

A kind of polypeptide compound targeting PD-1 receptor, its preparation method and application technical field The invention belongs to the technical field of biomedicine, be specifically related to a class of polypeptide compounds with PD-1 receptor as target, Its preparation method and application. Background technique In recent years, including low back pain, arthritis, postoperative persistent pain, fibromyalgia, neuropathic diseases Chronic pain is a very common social problem today, with more than 20% of adults in developed countries suffering from chronic pain Painful Torment (J. Neurosci. 2021, 41, 855‑865). Although chronic pain is not fatal, it has not been well treated, giving society and economic burden. Although signal transduction between immune cells, glial cells, and neurons is now considered Essential to the initiation and maintenance of chronic pain, the vast majority of therapeutic drugs still target only neurons. Currently, opioids have been...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06C07K1/06C07K1/04A61K38/08A61P29/00
CPCC07K7/06A61P29/00A61K38/00Y02P20/55
Inventor 陈罡赵龙罗浩杨日云陆沐幸
Owner NANTONG UNIVERSITY
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