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Application of sodium channel blocker mu-TRTX-Ca1a as analgesic drug

A drug and amino acid technology, applied in the field of biomedicine, can solve problems such as painlessness and pain, and achieve good analgesic effect

Active Publication Date: 2020-01-21
HUNAN NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Gain-of-function mutations in Na1.7 channels cause neuropathic pain, including erythromelalgia, paroxysmal pain, and small fiber neuralgia; conversely, loss-of-function mutations in Na1.7 lead to nonfunctional channels Protein expression, which in turn leads to congenital analgesia

Method used

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  • Application of sodium channel blocker mu-TRTX-Ca1a as analgesic drug
  • Application of sodium channel blocker mu-TRTX-Ca1a as analgesic drug
  • Application of sodium channel blocker mu-TRTX-Ca1a as analgesic drug

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Embodiment Construction

[0017] 1. Separation and purification of μ-TRTX-Ca1a

[0018] The isolation and purification of μ-TRTX-Ca1a was divided into two steps: (1) Preparative reverse-phase HPLC high-performance liquid chromatography: 300 mg of lyophilized spider venom was dissolved in ddH 2 O, formulated at 5 mg / ml. The sample is loaded on a C18 column of reverse phase high performance chromatography, and the elution system composed of water (containing 0.1% trifluoroacetic acid) and acetonitrile (containing 0.1% trifluoroacetic acid) is used for gradient elution, and the concentration of acetonitrile varies from 10% to 55%. , the elution gradient is 1% / min, the elution speed is 3ml / min, the detection wavelength is 280 / 215nm, and the target components are collected and freeze-dried. (2) Further separation and purification by analytical reverse-phase HPLC high-performance liquid chromatography: the lyophilized target component was washed with ddH 2 O, formulated at 0.5 mg / ml. Load the sample on a ...

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Abstract

The invention relates to an amino acid sequence and a gene sequence of cyriopagopus albostriatus toxin mu-TRTX-Ca1a, and application, and belongs to the field of biomedicine. The mu-TRTX-Ca1a contains38 amino acid residues, wherein six cysteines form three pairs of disulfide bonds, and the molecular weight is 4289.31 Da. The cyriopagopus albostriatus toxin mu-TRTX-Ca1a can preferentially inhibitsodium channel subtype Nav1.7. The cyriopagopus albostriatus toxin mu-TRTX-Ca1a can remarkably alleviate the pain caused by a mice formalin model, an acetic acid writhing model and a hot plate model,and can be used as a drug for treating pain.

Description

technical field [0001] The present invention relates to the discovery and application of the toxin μ-TRTX-Ca1a of the spider spider polypeptide, and belongs to the technical field of biomedicine. Background technique [0002] Voltage-gated ion channels are transmembrane proteins involved in cell electrical signal transduction, and are the basic excitatory units on the cell membranes of nerves, muscles, glands, etc. They can generate and transmit electrical signals, and their activities are related to cell excitation, contraction, Specific functions such as secretion and synaptic transmission are closely related. Among all mammalian sodium channel subtypes, Nav1.7, Nav1.8 and Nav1.9 are mainly distributed in the peripheral nervous system and participate in the transmission of pain signals, and Nav1.7 is currently one of the most promising targets for chronic pain relief . Gain-of-function mutations in Na1.7 channels cause neuropathic pain, including erythromelalgia, paroxys...

Claims

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Application Information

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IPC IPC(8): C07K14/435A61K38/17A61P29/00
CPCC07K14/43518A61P29/00A61K38/00
Inventor 容明强刘中华张云霄
Owner HUNAN NORMAL UNIVERSITY
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